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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Regulation of co-transcriptional splicing by RNA-binding protein PTBP1

ABSTRACT: We examined the role of PTBP1 in regulation of co-transcriptional splicing process by depleting this RNA-binding protein from embryonic stem cells using the auxin-inducible degron technology and analysing the total and chromatin-associated RNA fractions by RNA-seq. We also performed mNET-seq and ChIP-seq analyses using RNA polymerase II- and PTBP1-specific antibodies, respectively. Our data suggest that PTBP1 activates co-transcriptional splicing of hundreds of introns, a surprising effect given that PTBP1 is better known as a splicing repressor. Importantly, some co-transcriptionally activated introns fail to be spliced post-transcriptionally without PTBP1. In a striking example of this regulation, lasting retention of a PTBP1-dependent intron triggers nonsense-mediated decay of mRNAs encoding DNA methyltransferase DNMT3B, explaining their natural expression dynamics in development. Our further analyses suggest that this mechanism may protect differentiation-specific genes from aberrant methylation. We conclude that PTBP1-activated co-transcriptional splicing underlies biologically important decisions.

INSTRUMENT(S): Illumina NovaSeq 6000, Illumina HiSeq 4000

ORGANISM(S): Mus musculus

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PROVIDER: E-MTAB-11544 | biostudies-arrayexpress |

SECONDARY ACCESSION(S): ERP136320

REPOSITORIES: biostudies-arrayexpress

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