Steven Siqing Wang

The PPP2R1B gene, which encodes the beta isoform of the A subunit of the serine/threonine protein phosphatase 2A (PP2A), was identified as a putative human tumor suppressor gene. Sequencing of the PPP2R1B gene, located on human chromosome 11q22-24, revealed somatic alterations in 15% (5 out of 33) of primary lung tumors, 6% (4 out of 70) of lung tumor-derived cell lines, and 15% (2 out of 13) of primary colon tumors. One deletion mutation generated a truncated PP2A-Abeta protein that was unable to bind to the catalytic subunit of the PP2A holoenzyme. The PP2R1B gene product may suppress tumor development through its role in cell cycle regulation and cellular growth control.

11q23-24 chromosome is a region containing frequent allelic loss (loss of heterozygosity; LOH) in human cancers. To examine cancer-related allelic loss in the region between D11S940 and APOC3, we used 17 polymorphic markers and allotyped 28 lung cancer-derived cell lines and their corresponding matched lymphoblastoid cell lines. LOH was found in 71.4% (20/28) of the lung cancer cell lines and was localized to two distinct minimal regions of loss. One region is bracketed by markers D11S1647 and NCAM2 and contains the gene encoding the beta isoform of the A subunit of the human protein phosphatase 2A (PPP2R1B). Recently, mutations in this gene were described in lung and colon cancers, suggesting that PPP2R1B functions as a tumor-suppressor gene. A second minimal region of loss was defined between markers D11S1792 and D11S1885, a region estimated to be less than I Mb. Thus, chromosome 11 likely harbors two sites of suppressor oncogene activity in lung cancer, one defined by the PPP2R1B gene and the second located telomeric to PPP2R1B. This study facilitates the identification and cloning of a second critical tumor-suppressor gene involved in lung cancer, and possibly a variety of other cancers, on human chromosome band 11q23.

The reading frame in the mRNA for the cytochrome b apoprotein in mitochondria of Physarum polycephalum is created by the insertion of 43 nucleotides in the mRNA relative to the mtDNA sequence encoding it (RNA editing). Most of these insertions (31) are single cytidines; however, single uridines are inserted at six sites, and the dinucleotides, CU and GC, are inserted at two sites and one site, respectively. These insertions create a 392-codon reading frame in the mature mRNA. The amino acid sequence inferred from this reading frame has similarity to cytochromeb apoproteins encoded by other mtDNAs. The insertions are quite evenly distributed throughout the length of the reading frame with an average spacing of 27 nucleotides. This mRNA has the highest percentage (23%) of noncytidine insertions of anyPhysarum RNA characterized to date. cDNAs corresponding to partially edited RNAs can be enriched by selective amplification. Some cDNAs that lack the GC dinucleotide insertion are fully edited at sites flanking the GC dinucleotide insertion site. Similarly some cDNAs lack the CT dinucleotide insertion or have a CC or TT insertion flanked by a fully edited sequence. These results imply that dinucleotide editing occurs by a process separate from the global insertion of cytidines. The reading frame in the mRNA for the cytochrome b apoprotein in mitochondria of Physarum polycephalum is created by the insertion of 43 nucleotides in the mRNA relative to the mtDNA sequence encoding it (RNA editing). Most of these insertions (31) are single cytidines; however, single uridines are inserted at six sites, and the dinucleotides, CU and GC, are inserted at two sites and one site, respectively. These insertions create a 392-codon reading frame in the mature mRNA. The amino acid sequence inferred from this reading frame has similarity to cytochromeb apoproteins encoded by other mtDNAs. The insertions are quite evenly distributed throughout the length of the reading frame with an average spacing of 27 nucleotides. This mRNA has the highest percentage (23%) of noncytidine insertions of anyPhysarum RNA characterized to date. cDNAs corresponding to partially edited RNAs can be enriched by selective amplification. Some cDNAs that lack the GC dinucleotide insertion are fully edited at sites flanking the GC dinucleotide insertion site. Similarly some cDNAs lack the CT dinucleotide insertion or have a CC or TT insertion flanked by a fully edited sequence. These results imply that dinucleotide editing occurs by a process separate from the global insertion of cytidines. RNA editing is defined as the insertion, deletion, or substitution of nucleotides in an RNA such that the sequence of the RNA is different from that of the DNA encoding it (1Benne R. Van Den Burg J. Brakenhoff J. Sloof P. Van Bloom J. Tromp M. Cell. 1986; 46: 819-826Abstract Full Text PDF PubMed Scopus (603) Google Scholar). A unique type of RNA editing is found in mitochondria of the acellular slime mold Physarum polycephalum. In this organism most of the RNA editing sites are single cytidine (C) insertions, but occasional single uridine (U) insertions and dinucleotide (AA, AU, CU, and GU) insertions are also observed (2Mahendran R. Spottswood M.R. Miller D.L. Nature. 1991; 349: 434-438Crossref PubMed Scopus (114) Google Scholar, 3Miller D. Mahendran R. Spottswood M. Ling M. Wang S. Yang N. Costandy H. Benne R. RNA Editing: The Alteration of Protein Coding Sequences of RNA. Ellis Horwood, London1993: 87-101Google Scholar, 4Miller D. Mahendran R. Spottswood M. Costandy H. Wang S. Ling M. Yang N. Semin. Cell Biol. 1993; 4: 261-266Crossref PubMed Scopus (39) Google Scholar, 5Miller D. Mahendran R. Spottswood M. Ling M. Wang S. Yang N. Costandy H. Brennicke A. Kuck U. Plant Mitochondria. VCH, Weinheim, Germany1993: 53-62Google Scholar, 6Gott J.M. Visomirski L.M. Hunter J.L. J. Biol. Chem. 1993; 268: 25483-25486Abstract Full Text PDF PubMed Google Scholar, 7Mahendran R. Spottswood M.R. Ghate A. Ling M.-L. Jeng K. Miller D.L. EMBO J. 1994; 13: 232-240Crossref PubMed Scopus (55) Google Scholar, 8Rundquist B.A. Gott J.M. Mol. Gen. Genet. 1995; 247: 306-311Crossref PubMed Scopus (18) Google Scholar, 9Antes T.J. Costandy H. Mahendran R. Spottswood M. Miller D.L. Mol. Cell. Biol. 1998; 18: 7521-7527Crossref PubMed Google Scholar), as well as C to U substitutional editing (6Gott J.M. Visomirski L.M. Hunter J.L. J. Biol. Chem. 1993; 268: 25483-25486Abstract Full Text PDF PubMed Google Scholar). The locations of these editing sites are quite evenly distributed throughout the RNA with an average separation of about 25 nucleotides in mRNA and 45 nucleotides in rRNA. In Physarummitochondria, RNA editing has been observed in all of the three RNA types: mRNA (2Mahendran R. Spottswood M.R. Miller D.L. Nature. 1991; 349: 434-438Crossref PubMed Scopus (114) Google Scholar, 5Miller D. Mahendran R. Spottswood M. Ling M. Wang S. Yang N. Costandy H. Brennicke A. Kuck U. Plant Mitochondria. VCH, Weinheim, Germany1993: 53-62Google Scholar, 6Gott J.M. Visomirski L.M. Hunter J.L. J. Biol. Chem. 1993; 268: 25483-25486Abstract Full Text PDF PubMed Google Scholar), tRNA (9Antes T.J. Costandy H. Mahendran R. Spottswood M. Miller D.L. Mol. Cell. Biol. 1998; 18: 7521-7527Crossref PubMed Google Scholar), and rRNA (7Mahendran R. Spottswood M.R. Ghate A. Ling M.-L. Jeng K. Miller D.L. EMBO J. 1994; 13: 232-240Crossref PubMed Scopus (55) Google Scholar). RNA editing is required for gene expression because it produces a continuous open reading frame in mRNAs and produces conserved primary sequences and secondary structures in tRNAs and rRNAs. In contrast to trypanosome editing in which only uridines are inserted (10Stuart K. Allen T.E. Heidmann S. Seiwert S.D. Microbial. Mol. Biol. Rev. 1997; 61: 105-120Crossref PubMed Scopus (140) Google Scholar), in Physarum mitochondria any of the four nucleotides can be inserted but only in certain combinations (2Mahendran R. Spottswood M.R. Miller D.L. Nature. 1991; 349: 434-438Crossref PubMed Scopus (114) Google Scholar, 5Miller D. Mahendran R. Spottswood M. Ling M. Wang S. Yang N. Costandy H. Brennicke A. Kuck U. Plant Mitochondria. VCH, Weinheim, Germany1993: 53-62Google Scholar, 6Gott J.M. Visomirski L.M. Hunter J.L. J. Biol. Chem. 1993; 268: 25483-25486Abstract Full Text PDF PubMed Google Scholar, 7Mahendran R. Spottswood M.R. Ghate A. Ling M.-L. Jeng K. Miller D.L. EMBO J. 1994; 13: 232-240Crossref PubMed Scopus (55) Google Scholar, 8Rundquist B.A. Gott J.M. Mol. Gen. Genet. 1995; 247: 306-311Crossref PubMed Scopus (18) Google Scholar, 9Antes T.J. Costandy H. Mahendran R. Spottswood M. Miller D.L. Mol. Cell. Biol. 1998; 18: 7521-7527Crossref PubMed Google Scholar). Cytidines and uridines can be inserted as single nucleotides or members of certain dinucleotides (for example, AU, GU, and CU). Adenosine and guanosine have only been observed to be inserted as members of a dinucleotide insert (for example, AA and AU for adenosine and GU for guanosine). The fact that dinucleotide insertions are not just adjacent single nucleotide insertions is indicated by both editing site distribution and by the composition of the dinucleotide inserts. If dinucleotide insertions were produced by the occasional placement of two single insertion sites at adjacent positions, then the composition of the dinucleotide sites would reflect the composition of the single nucleotide insertion sites. This is clearly not the case because adenosine and guanosine nucleotides have only been observed to be inserted at dinucleotide insertion sites and because CC insertions, the type of dinucleotide insertion predicted to be most common based on single insertion nucleotide frequency, are not normally observed inPhysarum RNA. In addition, analysis of editing site distribution reveals an apparent constraint on how close together single nucleotide editing sites can be. No two sites have been observed to be separated by fewer than nine nucleotides (3Miller D. Mahendran R. Spottswood M. Ling M. Wang S. Yang N. Costandy H. Benne R. RNA Editing: The Alteration of Protein Coding Sequences of RNA. Ellis Horwood, London1993: 87-101Google Scholar). In terms of their relationship to single nucleotide insertions, dinucleotides could be inserted in several ways. For example: 1) All nucleotides could be inserted by the same process, independent of their identity or whether they are inserted as mono- or dinucleotides. 2) Nucleotides could be inserted by type at specific sites, such that one type of nucleotide is first inserted at a heterodinucleotide insertion site and then a second nucleotide is inserted to complete the site. This would also predict that single cytidines would be inserted separately from single uridines. The order in which nucleotide types are inserted could be sequential or random. 3) Dinucleotides could be inserted in a separate process from the insertion of mononucleotides. This would predict that cytidines and uridines in heterodinucleotides would be inserted separately from the insertion of cytidines or uridines as single nucleotides. These different modes of dinucleotide insertion would result in different patterns of nucleotide insertions in cDNAs corresponding to partially edited RNAs. By isolating and examining cDNAs corresponding to partially edited RNAs, these modes of dinucleotide editing can be distinguished. RNA editing in Physarum is very efficient as judged by the frequency at which insertions are present at potential editing sites in steady state RNA (3Miller D. Mahendran R. Spottswood M. Ling M. Wang S. Yang N. Costandy H. Benne R. RNA Editing: The Alteration of Protein Coding Sequences of RNA. Ellis Horwood, London1993: 87-101Google Scholar, 4Miller D. Mahendran R. Spottswood M. Costandy H. Wang S. Ling M. Yang N. Semin. Cell Biol. 1993; 4: 261-266Crossref PubMed Scopus (39) Google Scholar, 5Miller D. Mahendran R. Spottswood M. Ling M. Wang S. Yang N. Costandy H. Brennicke A. Kuck U. Plant Mitochondria. VCH, Weinheim, Germany1993: 53-62Google Scholar, 6Gott J.M. Visomirski L.M. Hunter J.L. J. Biol. Chem. 1993; 268: 25483-25486Abstract Full Text PDF PubMed Google Scholar, 8Rundquist B.A. Gott J.M. Mol. Gen. Genet. 1995; 247: 306-311Crossref PubMed Scopus (18) Google Scholar). In the mRNA of ATP synthase, the frequency of editing sites without a nucleotide insertion is lower than 5% (3Miller D. Mahendran R. Spottswood M. Ling M. Wang S. Yang N. Costandy H. Benne R. RNA Editing: The Alteration of Protein Coding Sequences of RNA. Ellis Horwood, London1993: 87-101Google Scholar, 4Miller D. Mahendran R. Spottswood M. Costandy H. Wang S. Ling M. Yang N. Semin. Cell Biol. 1993; 4: 261-266Crossref PubMed Scopus (39) Google Scholar, 5Miller D. Mahendran R. Spottswood M. Ling M. Wang S. Yang N. Costandy H. Brennicke A. Kuck U. Plant Mitochondria. VCH, Weinheim, Germany1993: 53-62Google Scholar). One possible explanation for this efficiency is that editing in Physarum occurs at or very near the mitochondrial transcription complex so that nascent transcripts are edited as an early step in mitochondrial gene expression. Consistent with this idea Visomirski-Robic and Gott (11Visomirski-Robic L. Gott J.M. Proc. U. S. A. 1997; PubMed Scopus (31) Google Scholar, L. Gott J.M. RNA. 1997; Google have that in mitochondria in which one of the is RNA editing has very close to the mitochondrial RNA cDNAs corresponding to RNAs that are partially edited have been (9Antes T.J. Costandy H. Mahendran R. Spottswood M. Miller D.L. Mol. Cell. Biol. 1998; 18: 7521-7527Crossref PubMed Google Scholar, L. Gott J.M. RNA. 1997; Google Scholar). these RNAs are RNA editing or edited of the editing process, their nucleotide insertion about the in which nucleotides are inserted inPhysarum mitochondrial RNAs. these RNAs are cDNAs corresponding to have been to that the Physarum mitochondrial mRNA is This editing not only single cytidine insertions but also a of single uridine insertions as well as three dinucleotide insertions, one of which has not been also a to and b cytochrome cDNAs of very partially edited mRNAs that about the relationship of dinucleotide and P. polycephalum characterized at by R. of at from the were at 27 in the with continuous in Cell Scopus Google Scholar). were mtDNA from as by Mahendran R. Spottswood M.R. Yang Miller D.L. Genet. PubMed Scopus Google Scholar). were by and with three they were in a for The at for to and were from the by at The mitochondria were then by several of mitochondria were for RNA and DNA All for the of RNA were in RNA from mitochondria J. by in an of by three of and one The separated from the by at for RNA then with of and of and at were separated by on The in a a The The at with for The RNA to the by to for and the for at in were at in and the were in at 25 and in at were an DNA The were in and from mitochondria were with in the of and at for by by The were in with RNA and were in at for and then in the by the of and at for The cDNAs were as by S. R. PubMed Scopus Google Scholar). The cDNAs were in of and of the were to and then the with The and were as for for and for were For the and or were with and to to with insertions were by The were then DNA sequences were by the S. Proc. U. S. A. PubMed Scopus Google a S. DNA sequence analysis and amino acid sequence and were the sequence analysis PubMed Scopus Google Scholar). were first for GC insertion, for CU insertion for C insertion and then separated by on The at the of DNA and the DNA in the These were by the same The were with or and then as have a of mitochondrial that is to be Mahendran R. Spottswood M.R. Yang Miller D.L. Genet. PubMed Scopus Google Scholar). from this a RNA The mtDNA sequence of the for this RNA not a open reading of open reading frame amino acid sequences that are or to the sequence of cytochrome b from a of acid sequence indicated that were required to one continuous open reading frame with to that mitochondrial b mRNA is whether this the cDNAs were from and then of and mtDNA sequences reveals that the sequences from their mtDNA by the of nucleotides that for the are insertion sites. Most of are single C single U insertions as well as two types of dinucleotide insertion and are also AU, CU, and GU insertions have been observed in the mRNA for of cytochrome (6Gott J.M. Visomirski L.M. Hunter J.L. J. Biol. Chem. 1993; 268: 25483-25486Abstract Full Text PDF PubMed Google Scholar, 8Rundquist B.A. Gott J.M. Mol. Gen. Genet. 1995; 247: 306-311Crossref PubMed Scopus (18) Google Scholar), and CU and AA dinucleotide insertions have been in the rRNA of Physarum mitochondria (7Mahendran R. Spottswood M.R. Ghate A. Ling M.-L. Jeng K. Miller D.L. EMBO J. 1994; 13: 232-240Crossref PubMed Scopus (55) Google Scholar), this is the first of a GC dinucleotide This GC dinucleotide insertion a second in which can be inserted in Physarum RNA together with the of AA and AU dinucleotide insertions (7Mahendran R. Spottswood M.R. Ghate A. Ling M.-L. Jeng K. Miller D.L. EMBO J. 1994; 13: 232-240Crossref PubMed Scopus (55) Google Scholar, 8Rundquist B.A. Gott J.M. Mol. Gen. Genet. 1995; 247: 306-311Crossref PubMed Scopus (18) Google and C and U insertions (2Mahendran R. Spottswood M.R. Miller D.L. Nature. 1991; 349: 434-438Crossref PubMed Scopus (114) Google Scholar, 5Miller D. Mahendran R. Spottswood M. Ling M. Wang S. Yang N. Costandy H. Brennicke A. Kuck U. Plant Mitochondria. VCH, Weinheim, Germany1993: 53-62Google Scholar, 6Gott J.M. Visomirski L.M. Hunter J.L. J. Biol. Chem. 1993; 268: 25483-25486Abstract Full Text PDF PubMed Google Scholar, 7Mahendran R. Spottswood M.R. Ghate A. Ling M.-L. Jeng K. Miller D.L. EMBO J. 1994; 13: 232-240Crossref PubMed Scopus (55) Google Scholar, 9Antes T.J. Costandy H. Mahendran R. Spottswood M. Miller D.L. Mol. Cell. Biol. 1998; 18: 7521-7527Crossref PubMed Google Scholar), that any of the four nucleotides can be inserted in Physarum RNAs. the in which these nucleotides can be inserted to be All three dinucleotide insertions are at sites flanked by one or nucleotides that are the same as the inserted nucleotides. This results in a sequence in which it is which of several nucleotides to the inserted This also it whether the dinucleotide insertion is GC or CU or This has been observed for other dinucleotide insertions as well (6Gott J.M. Visomirski L.M. Hunter J.L. J. Biol. Chem. 1993; 268: 25483-25486Abstract Full Text PDF PubMed Google Scholar, 7Mahendran R. Spottswood M.R. Ghate A. Ling M.-L. Jeng K. Miller D.L. EMBO J. 1994; 13: 232-240Crossref PubMed Scopus (55) Google Scholar, 8Rundquist B.A. Gott J.M. Mol. Gen. Genet. 1995; 247: 306-311Crossref PubMed Scopus (18) Google Scholar). The editing sites are evenly distributed throughout the sequence with an average separation of 27 nucleotides and a of nucleotides observed for other edited RNAs inPhysarum (2Mahendran R. Spottswood M.R. Miller D.L. Nature. 1991; 349: 434-438Crossref PubMed Scopus (114) Google Scholar, 6Gott J.M. Visomirski L.M. Hunter J.L. J. Biol. Chem. 1993; 268: 25483-25486Abstract Full Text PDF PubMed Google Scholar, 7Mahendran R. Spottswood M.R. Ghate A. Ling M.-L. Jeng K. Miller D.L. EMBO J. 1994; 13: 232-240Crossref PubMed Scopus (55) Google Scholar, 9Antes T.J. Costandy H. Mahendran R. Spottswood M. Miller D.L. Mol. Cell. Biol. 1998; 18: 7521-7527Crossref PubMed Google Scholar), is a for cytidine insertions to be of dinucleotides. the of of the cytidine insertions be to their insertion to an of cytidines are inserted or have the potential to be inserted a of the b mRNA that editing sites are to the open reading the average spacing editing sites is 27 nucleotides the reading editing sites were of the or of the were any editing sites for than nucleotides of the a reading frame is not required for editing because tRNAs and that lack open reading are also edited in Physarum (7Mahendran R. Spottswood M.R. Ghate A. Ling M.-L. Jeng K. Miller D.L. EMBO J. 1994; 13: 232-240Crossref PubMed Scopus (55) Google Scholar, 9Antes T.J. Costandy H. Mahendran R. Spottswood M. Miller D.L. Mol. Cell. Biol. 1998; 18: 7521-7527Crossref PubMed Google Scholar). This that editing sites are to sequences in Physarum six sites and single uridines are analysis of independent cDNAs uridine and not cytidine insertions at these sites. a single uridine insertion has been in the mRNA for of cytochrome (6Gott J.M. Visomirski L.M. Hunter J.L. J. Biol. Chem. 1993; 268: 25483-25486Abstract Full Text PDF PubMed Google Scholar), the rRNA (7Mahendran R. Spottswood M.R. Ghate A. Ling M.-L. Jeng K. Miller D.L. EMBO J. 1994; 13: 232-240Crossref PubMed Scopus (55) Google Scholar), and (9Antes T.J. Costandy H. Mahendran R. Spottswood M. Miller D.L. Mol. Cell. Biol. 1998; 18: 7521-7527Crossref PubMed Google Scholar), this is the highest of uridine insertions inPhysarum RNA to date. This of noncytidine insertions an to the relationship of these insertions to the cytidine The uridine insertions are not but are the cytidine insertion sites. of the uridine insertions are to a cytidine insertion than nine the observed cytidine insertion sites. These six uridine insertion sites the of uridine insertions in Physarum RNA to The uridine insertion sites from these RNAs have been in for In case one b site the uridine insertion is to one or uridines frequency than by and with one b site the uridine insertion could be of a than these not to be any similarity in the sequence the uridine insertion sites. of these 43 nucleotides an open reading frame of different types are created by C insertions, and four types are created by U the nine C insertion types in which the of the insertion can be four and have the C insertion at the first one has the C insertion at the second and four and have the C insertion at the The four types in which cytidine is inserted at the are and of the cytidine insertions in which the of the insertion can be The relative of the U insertions the be with one the insertions are to a U. The amino acid sequence from the open reading frame in the sequence to the cytochromeb apoprotein from mitochondria of A. J. Biol. Chem. Full Text PDF PubMed Google Scholar), S. J. B.A. R. Nature. PubMed Scopus Google Scholar), and EMBO J. PubMed Google All of the amino acid conserved in and are also present in the sequence inferred from the edited RNA These that the RNA is the b mRNA and that it is edited to a mRNA. Consistent with the of Physarum from the sequence is as from the of and as these sequences are from one the relationship of the GC dinucleotide insertion to the single cytidine insertions, a has been to and cDNAs corresponding to partially edited The insertion of the GC dinucleotide in mRNA an site in If the GC dinucleotide is not inserted or only one of the two nucleotides is this site be in cDNAs from this RNA the sequence six specific nucleotides and nine any of a of or insertions would result in the of the site in the for b cDNAs the site, cDNAs produced by from b mRNA that site were A first with to mtDNA and then as a for to flanking several editing sites the GC insertion site were to cDNAs from the These were with and the two were separated from the by on a all of the by This result that a percentage of in the steady state is edited at this site, with results from Gott (6Gott J.M. Visomirski L.M. Hunter J.L. J. Biol. Chem. 1993; 268: 25483-25486Abstract Full Text PDF PubMed Google Scholar, 8Rundquist B.A. Gott J.M. Mol. Gen. Genet. 1995; 247: 306-311Crossref PubMed Scopus (18) Google and Miller (3Miller D. Mahendran R. Spottswood M. Ling M. Wang S. Yang N. Costandy H. Benne R. RNA Editing: The Alteration of Protein Coding Sequences of RNA. Ellis Horwood, London1993: 87-101Google Scholar, 4Miller D. Mahendran R. Spottswood M. Costandy H. Wang S. Ling M. Yang N. Semin. Cell Biol. 1993; 4: 261-266Crossref PubMed Scopus (39) Google Scholar, 5Miller D. Mahendran R. Spottswood M. Ling M. Wang S. Yang N. Costandy H. Brennicke A. Kuck U. Plant Mitochondria. VCH, Weinheim, Germany1993: 53-62Google that the efficiency of nucleotide insertion at a editing site is than The from the and the DNA The DNA the same The were with a second to from in the first The were and In some were which insertions at any these from RNAs or from mtDNA which is not three independent which the site have insertions at editing sites. the editing sites, two independent which were fully edited at of the single cytidine insertion sites but the GC dinucleotide insertion and a different RNA and a different of that insertion sites single C insertions, two single U insertions, and two CU dinucleotide This also the GC insertion but fully These results that the cytidine of the GC dinucleotide insertion is not by the same process in which single cytidines are inserted and that the GC dinucleotide insertion occurs separately from of the CU dinucleotide a of the CU dinucleotide at site in b mRNA a site in This site is in cDNAs that lack one or both of the inserted nucleotides. were that produced an the first editing sites. insertions at editing sites adjacent to the CT dinucleotide insertion site but the CT dinucleotide This also a C insertion at site A second of a different RNA produced four unique cDNAs that the site to the CT insertion but fully edited at sites adjacent to the CT insertion site. In the editing for the CT of site as well as the C at the adjacent editing site nucleotides of the CU editing site. dinucleotide insertions that not create the site. In the dinucleotide insertion and in the dinucleotide insertion No with a single nucleotide inserted at the dinucleotide site. the with a substitution or an insertion at any other than at an editing site. These results that the cytidine and uridine of the CU dinucleotide insertion are not by the same in which single cytidines or single uridines are inserted and that the CU dinucleotide insertion occurs separately from site is created in cDNAs by a cytidine insertion at site for cDNAs that lack this site the produced that site. These were for the of the or the site, but of the that site the or site, that they the GC and CU dinucleotide analysis of of these sequences that to fully RNAs. types of corresponding to partially edited RNAs that be based on the dinucleotide were not cDNAs in which only one or both of the dinucleotide insertions is present in and cDNAs in which a cytidine is not inserted at site in fully edited to the in contrast to the of isolating the for a dinucleotide site partially edited sequences of cDNAs for the same RNA and for that and dinucleotide insertions are produced by a separate these results that the cDNAs reflect the RNA and are not an of the cDNAs corresponding to RNAs with certain editing patterns be because they are not in the RNA of cDNAs corresponding to partially edited RNAs that dinucleotide insertions are independent from cytidine insertions in that dinucleotide insertions can be in sequences fully edited at single cytidine and uridine sites. This is with the unique composition of the dinucleotide insertions and at some of from the process of single cytidine Visomirski-Robic and Gott (11Visomirski-Robic L. Gott J.M. Proc. U. S. A. 1997; PubMed Scopus (31) Google Scholar, L. Gott J.M. RNA. 1997; Google have that in mitochondria with of one nucleotide insertions can be in nascent RNAs at both single nucleotide and dinucleotide editing sites very close to the mitochondrial transcription it is that some editing can be with the transcription it is not whether editing is with nucleotides to the of the nascent RNA or with nucleotides inserted two nucleotides in the RNA. If editing is in this then it is that the partially edited RNAs are that have not been The fact that sequences were that have cytidine insertions but lack dinucleotide insertions, but not the that GC insertions global cytidine If editing is then partially edited cDNAs from RNAs in which editing to insert a nucleotide at a potential editing site. These RNAs would not be but would that dinucleotide insertions can be without cytidine A is that cytidine insertions are dinucleotide insertions are which would that dinucleotides are inserted by a separate from cytidine not a single nucleotide inserted at dinucleotide insertion sites, that the two nucleotides of a dinucleotide insertion are inserted at about the same Visomirski-Robic and Gott L. Gott J.M. RNA. 1997; Google have that RNA in mitochondria that were of can partially edited RNAs to the type by have that at of RNAs are produced that can lack the U at a CU insertion site but have the C inserted at this site. This that is the of the uridine insertions in heterodinucleotides as is for single cytidine insertion sites. of RNAs with a single nucleotide insertion at potential dinucleotide editing sites only in which a is In of which result in partially edited RNAs with C insertions at potential single cytidine editing sites, the CU dinucleotide editing site has both nucleotides inserted L. Gott J.M. RNA. 1997; Google Scholar). The fact that CU dinucleotide and single C nucleotide sites are by is with the editing of these two types of site cDNAs that the site nucleotide insertions but of the type to create the site. of the CT insertion found in most cDNAs at this site, these two cDNAs a CC or a TT insertion at the site. is not whether these cDNAs RNAs in which the nucleotide inserted or RNAs in which one of the nucleotides is to the sequence. Gott (6Gott J.M. Visomirski L.M. Hunter J.L. J. Biol. Chem. 1993; 268: 25483-25486Abstract Full Text PDF PubMed Google have observed four sites in the mRNA in which cytidines are to uridines. The of this in Physarum mitochondria to the idea that the CU could be produced by nucleotide The insertion of all four nucleotides to and tRNAs in mitochondria of Physarum this editing from all This could result from of nucleotide insertion or a single to an editing site and insert the and type of nucleotide at that The with the most noncytidine insertions of anyPhysarum RNA characterized to the of this of partially b mRNAs and of the editing of b mRNAs from other the of this unique type of RNA

11q23–24 chromosome is a region containing frequent allelic loss (loss of heterozygosity; LOH) in human cancers. To examine cancer-related allelic loss in the region between D11S940 and APOC3, we used 17 polymorphic markers and allotyped 28 lung cancer-derived cell lines and their corresponding matched lymphoblastoid cell lines. LOH was found in 71.4% (20/28) of the lung cancer cell lines and was localized to two distinct minimal regions of loss. One region is bracketed by markers D11S1647 and NCAM2 and contains the gene encoding the β isoform of the A subunit of the human protein phosphatase 2A (PPP2R1B). Recently, mutations in this gene were described in lung and colon cancers, suggesting that PPP2R1B functions as a tumor-suppressor gene. A second minimal region of loss was defined between markers D11S1792 and D11S1885, a region estimated to be less than 1 Mb. Thus, chromosome 11 likely harbors two sites of suppressor oncogene activity in lung cancer, one defined by the PPP2R1B gene and the second located telomeric to PPP2R1B. This study facilitates the identification and cloning of a second critical tumor-suppressor gene involved in lung cancer, and possibly a variety of other cancers, on human chromosome band 11q23. Genes Chromosomes Cancer 25:154–159, 1999. © 1999 Wiley-Liss, Inc.