SINEUP long non-coding RNA acts via PTBP1 and HNRNPK to promote translational initiation assemblies

Naoko Toki(RIKEN Center for Integrative Medical Sciences), Hazuki Takahashi(RIKEN Center for Integrative Medical Sciences), Harshita Sharma(RIKEN Center for Integrative Medical Sciences), Matthew Valentine(RIKEN Center for Integrative Medical Sciences), Mohammed Ferdous‐Ur Rahman(RIKEN Center for Integrative Medical Sciences), S. Zucchelli(Università degli Studi del Piemonte Orientale “Amedeo Avogadro”), Stefano Gustincich(Italian Institute of Technology), Piero Carninci(RIKEN Center for Integrative Medical Sciences)
Nucleic Acids Research
September 23, 2020
Cited by 79Open Access
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Abstract

SINEUPs are long non-coding RNAs (lncRNAs) that contain a SINE element, and which up-regulate the translation of target mRNA. They have been studied in a wide range of applications, as both biological and therapeutic tools, although the underpinning molecular mechanism is unclear. Here, we focused on the sub-cellular distribution of target mRNAs and SINEUP RNAs, performing co-transfection of expression vectors for these transcripts into human embryonic kidney cells (HEK293T/17), to investigate the network of translational regulation. The results showed that co-localization of target mRNAs and SINEUP RNAs in the cytoplasm was a key phenomenon. We identified PTBP1 and HNRNPK as essential RNA binding proteins. These proteins contributed to SINEUP RNA sub-cellular distribution and to assembly of translational initiation complexes, leading to enhanced target mRNA translation. These findings will promote a better understanding of the mechanisms employed by regulatory RNAs implicated in efficient protein translation.


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