Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA338698 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4020950.fastq.gz | Fastqsanger.gz | |||
| SRR4020949.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 2 of 2 |
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Project description:The cellular accumulation of short non-coding RNAs (ncRNAs) transcribed by RNA Polymerase III (Pol III) is a hallmark of various cellular stressors and inflammatory-associated diseases. Yet, the mechanisms driving the accumulation of these RNAs are largely undefined. Infection with several DNA viruses is known to significantly alter the cellular Pol III transcriptome, leading to the induction of a class of non-coding retrotransposons known as short interspersed nuclear elements (SINE) and tRNA genes. Here, we sought to define the mechanisms driving Pol III transcribed ncRNA abundance during viral infection, using the murine herpesvirus MHV68 as a model. Our findings reveal that while the expression of Pol III transcripts, such as the murine-specific family of B2 SINE ncRNAs and pre-tRNAs, significantly increase during MHV68 infection, Pol III genomic occupancy is enhanced at a much fewer subset of B2 SINE and tRNA genes. Using DNA motif analyses and a convolutional neural network (CNN) based model, we identified non-promoter sequence elements within B2 SINE genes that distinguish infection-induced loci. We found that infection-induced B2 SINE genes are enriched for signal sequences that confer polyadenylation, and endogenous B2 SINE ncRNA polyadenylation depends on mRNA cleavage and polyadenylation (CPSF) machinery. We discovered that mRNA CPSF components are recruited to sites of Pol III transcription in response to MHV68 infection in a manner dependent on Pol III occupancy. Chromatin-associated B2 SINE ncRNAs are also bound by the CPSF complex, suggesting an RNA-dependent, co-transcriptional polyadenylation of B2 SINE ncRNAs. This uncovers an inducible, coupled relationship between Pol III transcription and mRNA-like polyadenylation of ncRNAs. Also, CPSF recruitment to Pol III genes is not restricted to murine genomes but also occurs at human SINE and tRNA genes, suggesting that this previously unknown coupled relationship may be a widespread feature of Pol III transcription.
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Project description:Short interspersed nuclear elements (SINEs) are retrotransposons evolutionarily derived from endogenous RNA Polymerase III RNAs. Though SINE elements have undergone exaptation into gene regulatory elements, how transcribed SINE RNA impacts transcriptional and post-transcriptional regulation is largely unknown. This is partly due to a lack of information regarding which of the loci have transcriptional potential. Here, we present an approach (short interspersed nuclear element sequencing, SINE-seq), which selectively profiles RNA Polymerase III-derived SINE RNA, thereby identifying transcriptionally active SINE loci. Applying SINE-seq to monitor murine B2 SINE expression during a gammaherpesvirus infection revealed transcription from 28,270 SINE loci, with ~50% of active SINE elements residing within annotated RNA Polymerase II loci. Furthermore, B2 RNA can form intermolecular RNA-RNA interactions with complementary mRNAs, leading to nuclear retention of the targeted mRNA via a mechanism involving p54nrb. These findings illuminate a pathway for the selective regulation of mRNA export during stress via retrotransposon activation.
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