Azzurra Codino

Long Interspersed Nuclear Elements-1s (L1s) are transposable elements that constitute most of the genome's transcriptional output yet have still largely unknown functions. Here we show that L1s are required for proper mouse brain corticogenesis operating as regulatory long non-coding RNAs. They contribute to the regulation of the balance between neuronal progenitors and differentiation, the migration of post-mitotic neurons and the proportions of different cell types. In cortical cultured neurons, L1 RNAs are mainly associated to chromatin and interact with the Polycomb Repressive Complex 2 (PRC2) protein subunits enhancer of Zeste homolog 2 (Ezh2) and suppressor of zeste 12 (Suz12). L1 RNA silencing influences PRC2's ability to bind a portion of its targets and the deposition of tri-methylated histone H3 (H3K27me3) marks. Our results position L1 RNAs as crucial signalling hubs for genome-wide chromatin remodelling, enabling the fine-tuning of gene expression during brain development and evolution.

The planarian Schmidtea mediterranea is being studied as a model species for regeneration, but the assembly of planarian genomes remains challenging. Here, we report a high-quality haplotype-phased, chromosome-scale genome assembly of the sexual S2 strain of S. mediterranea and high-quality chromosome-scale assemblies of its three close relatives, S. polychroa, S. nova, and S. lugubris. Using hybrid gene annotations and optimized ATAC-seq and ChIP-seq protocols for regulatory element annotation, we provide valuable genome resources for the planarian research community and a first comparative perspective on planarian genome evolution. Our analyses reveal substantial divergence in protein-coding sequences and regulatory regions but considerable conservation within promoter and enhancer annotations. We also find frequent retrotransposon-associated chromosomal inversions and interchromosomal translocations within the genus Schmidtea and, remarkably, independent and nearly complete losses of ancestral metazoan synteny in Schmidtea and two other flatworm groups. Overall, our results suggest that platyhelminth genomes can evolve without syntenic constraints.

mouse allele and applied the highly stringent cross-linking and analysis of cDNAs to define NANOS2 RNA occupancy in SSC lines. NANOS2 recognizes the AUKAAWU consensus motif, mostly found in the 3' untranslated region of defined messenger RNAs (mRNAs). We find that NANOS2 is a regulator of key signaling and metabolic pathways whose dosage or activity are known to be critical for SSC maintenance. NANOS2 interacts with components of CCR4-NOT deadenylase complex in SSC lines, and consequently, NANOS2 binding reduces the half-lives of target transcripts. In summary, NANOS2 contributes to SSC maintenance through the regulation of target mRNA stability and key self-renewal pathways.

Post-synthesis modification of biomolecules is an efficient way of regulating and optimizing their functions. The human epitranscriptome includes a variety of more than 100 modifications known to exist in all RNA subtypes. Modifications of non-coding RNAs are particularly interesting since they can directly affect their structure, stability, interaction and function. Indeed, non-coding RNAs such as tRNA and rRNA are the most modified RNA species in eukaryotic cells. In the last 20 years, new functions of non-coding RNAs have been discovered and their involvement in human disease, including cancer, became clear. In this review, we will present the evidence connecting modifications of different non-coding RNA subtypes and their role in cancer.

Abstract The planarian Schmidtea mediterranea can regenerate its entire body from small tissue fragments and is studied as regeneration model species. The assembly and functional analysis of planarian genomes has proven challenging due its high A/T content (70% A/T), repetitive nature, and limited transferability of routine laboratory protocols due to their divergent biochemistry. Only few and often fragmented genome assemblies are currently available, and open challenges include the provision of well-annotated chromosome-scale reference assemblies of the model species and other planarians for a comparative genome evolution perspective. Here we report a haplotype-phased, chromosome-scale genome assembly and high-quality gene annotations of the sexual S2 strain of S. mediterranea and provide putative regulatory region annotations via optimized ATAC-seq and ChIP-seq protocols. To additionally leverage sequence conservation for regulatory element annotations, we generated chromosome-scale genome assemblies and chromatin accessibility data for the three closest relatives of S. mediterranea : S. polychroa , S. nova , and S. lugubris . We find substantial divergence in protein-coding sequences and regulatory regions, yet reveal remarkable conservation in ChIP-mark bearing open chromatin regions identified as promoters and enhancers in S. mediterranea . The resulting high-confidence set of evolutionary conserved enhancers and promoters provides a valuable resource for the analysis of gene regulatory circuits and their evolution within the taxon. In addition, our four chromosome-scale genome assemblies provide a first comparative perspective on planarian genome evolution. Our analyses reveal frequent retrotransposon-associated chromosomal inversions and inter-chromosomal translocations that lead to a degradation of synteny across the genus. Interestingly, we further find independent and near-complete losses of the ancestral metazoan synteny across Schmidtea and two other flatworm groups, indicating that platyhelminth genomes largely evolve without syntenic constraints. Our work provides valuable genome resources for the planarian research community and sets a foundation for the comparative genomics of planarians. We reveal a contrast between the fast structural evolution of planarian genomes and the conservation of their regulatory elements, suggesting a unique genome evolution in flatworms where gene positioning may not be essential.