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Sex-lethal is recruited to chromatin to promote neuronal tRNA synthesis in males through RNA Polymerase III regulation

ABSTRACT: Sex-lethal is recruited to chromatin to promote neuronal tRNA synthesis in males through RNA Polymerase III regulation

PROVIDER: PRJNA1251667 | ENA |

REPOSITORIES: ENA

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Sex-lethal is recruited to chromatin to promote neuronal tRNA synthesis in males through RNA Polymerase III regulation [RNA-seq]

Project description:Sex-lethal is recruited to chromatin to promote neuronal tRNA synthesis in males through RNA Polymerase III regulation [RNA-seq]

| PRJNA1251671 | ENA

Sex-lethal is recruited to chromatin to promote neuronal tRNA synthesis in males through RNA Polymerase III regulation [small RNA-seq]

Project description:Sex-lethal is recruited to chromatin to promote neuronal tRNA synthesis in males through RNA Polymerase III regulation [small RNA-seq]

| PRJNA1251672 | ENA

Sex-lethal is recruited to chromatin to promote neuronal tRNA synthesis in males through RNA Polymerase III regulation [RNA-seq]

Project description:The RNA-binding protein sex-lethal (Sxl) is classically defined as a master regulator of sex determination and RNA splicing in Drosophila melanogaster. However, this role is not conserved in all species and functions beyond this canonical pathway remain largely unexplored. Here, we uncover a splicing-independent function for Sxl at the chromatin level in the Drosophila brain. Using Targeted DamID (TaDa) profiling in larval neurons, we identify widespread recruitment of Sxl to promoter regions, independent of sex and RNA binding activity. Notably, Sxl chromatin occupancy exhibits near-complete overlap with Polr3E (RPC37), an RNA Polymerase III subunit, with Sxl binding abolished upon Polr3E knockdown. Depletion of Sxl in mature male neurons equally induces widespread transcriptional changes, particularly in metabolic genes, and improves negative geotaxis during ageing, phenotypes that closely mirror Polr3E knockdown. Conversely, overexpression of SxlRAC isoform enhances tRNA synthesis and upregulates metabolic gene expression. Together, these findings reveal a previously unrecognised role for Sxl in regulating Pol III activity via Polr3E, promoting tRNA synthesis and supporting neuronal metabolism. Given the emerging tie between Pol III regulation and neuronal ageing, our study highlights Sxl as a novel modulator of neuronal homeostasis.

2025-04-18 | GSE294835 | GEO

Sex-lethal is recruited to chromatin to promote neuronal tRNA synthesis in males through RNA Polymerase III regulation [small RNA-seq]

2025-04-18 | GSE294837 | GEO

Sex-lethal is recruited to chromatin to promote neuronal tRNA synthesis in males through RNA Polymerase III regulation

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-04-18 | GSE294838 | GEO

Sex Lethal is recruited to chromatin by RNA polymerase III [DamID-seq]

Project description:We discovered that the splicing factor Sex lethal (Sxl) also associates strongly with chromatin and that this association is not linked to its RNA-binidng capacity, nor its N- or C-terminal domains. We also found that Sxl is recruited to chromatin by the RNA polymerase III subunt Polr3E.

2025-04-18 | GSE239790 | GEO

Sex Lethal is recruited to chromatin by RNA polymerase III [DamID-seq]

Project description:Sex Lethal is recruited to chromatin by RNA polymerase III [DamID-seq]

| PRJNA1000971 | ENA

Cdk1 Gates Cell Cycle-Dependent tRNA Synthesis by Regulating RNA Polymerase III Activity

Project description:tRNA genes are transcribed by RNA polymerase III (RNAPIII). During recent years it has become clear that RNAPIII activity is strictly regulated by the cell in response to environmental cues and the homeostatic status of the cell. However, the molecular mechanisms that control RNAPIII activity to regulate the amplitude of tDNA transcription in normally cycling cells are not well understood. Here, we show that tRNA levels fluctuate during the cell cycle and reveal the underlying molecular mechanism. The cyclin Clb5 recruits the cyclin dependent kinase Cdk1 to tRNA genes to boost tDNA transcription during S phase. At tDNA genes, Cdk1 promotes the recruitment of TFIIIC, stimulates the interaction between TFIIIB and TFIIIC, and increases the dynamics of RNA polymerase III in vivo. Furthermore, we identified Bdp1 as an important Cdk1 substrate in this process. Preventing Bdp1 phosphorylation prevented cell cycle-dependent recruitment of TFIIIC and abolished the cell cycle-induced increase in tDNA transcription. Our findings demonstrate that under optimal growth conditions Cdk1 gates tRNA synthesis in S phase by regulating the RNAPIII machinery, revealing a direct link between the cell cycle and RNAPIII activity.

2018-10-19 | PXD011084 | Pride

Global analysis of transcriptionally engaged yeast RNA polymerase III reveals extended tRNA transcripts

Project description:RNA polymerase III (RNAPIII) synthesizes a range of highly abundant small stable RNAs, principally pre-tRNAs. Here we report the genome-wide analysis of nascent transcripts attached to RNAPIII under permissive and restrictive growth conditions. This revealed strikingly uneven polymerase distributions across transcription units, generally with a predominant 5Â´ peak. This peak was higher for more heavily transcribed genes, suggesting that initiation site clearance is rate limiting during RNAPIII transcription. Down-regulation of RNAPIII transcription under stress conditions was found to be uneven; a subset of tRNA genes showed low response to nutrient shift or loss of the major transcription regulator Maf1, suggesting potential âhousekeepingâ roles. Many tRNA genes were found to generate long, 3Â´-extended forms due to read-through of the canonical poly(U) terminators. The degree of read-through was anti-correlated with the density of T-residues in the coding strand, and multiple, functional terminators can be located far downstream. The steady-state levels of 3Â´-extended pre-tRNA transcripts are low, apparently due to targeting by the nuclear surveillance machinery; especially the RNA-binding protein Nab2, cofactors for the nuclear exosome and the 5Â´-exonuclease Rat1. CRAC protocol performed on samples containing HTP-tagged proteins: Rpc160(Rpo31), Nab2, Rrp44(Dis3), Rrp6 and Mtr4. Rpc-160-bound RNAs were analyzed in wildtype and maf1 mutant cells and after a shift to medium containing glycerol.

2016-05-18 | E-GEOD-77863 | biostudies-arrayexpress

RNAseq of old and young males with equal physical activity

Project description:18 older (65-71 years) and 20 young (19-25 years) males were recruited based on similar, self-reported physical activity, which was verified using accelerometry measurements. Gene expression profiles of vastus lateralis biopsies obtained by RNA sequencing. A clear ageing signature was observed despite similar physcical activity.

2021-10-20 | GSE159217 | GEO

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