SR Proteins Mediated Transcription Regulation

Paused RNAP Ⅱ at gene promoters produces short nascent RNA of unknown function, and the transition to productive elongation requires active recruitment of the transcription elongation factor P-TEFb. On the HIV-1promoter, the virus-encoded protein Tat activates transcription elongation by relocating P-TEFb from the inhibitory7SK complex to promoter-escaped RNAP II via binding the TAR element in nascent viral RNA; however, it has been unclear whether cellular genes use an analogous mechanism to activate transcription. We present evidence that SC35(previously known as SRSF2, a prototypical SR family splicing factor) has functions related to Tat, and its binding sites in promoter-associated transcripts play roles equivalent to TAR in activating cellular genes by overcoming RNAP Ⅱ pausing near the transcription start. These findings reveal unanticipated transcription/splicing coupling, a function of promoter-proximal nascent RNA, and a unifying mechanism for transcription activation by viral and cellular genes.Different methods have been developed to mearsure the RNAP Ⅱ transcription rate. However, none of them reached to the genome wide level. Here we develope a novel method combined with GRO-seq technology, we mearsure the transcription rate globally in MEFs. Surprisingly, we find SC35depletion slows down the transcription rate, and decreases the transcriptional processivity in the gene body, which reveals a previous unanticipiated intimately splicing and transcription coupling mechanism.More and more evidence suggested that histone makers link splicing machinery to mediate pre-mRNA splicing, while the splicing machinery reversely regulates histone modifications is largely unknown. Here, we show that SC35depletion, increases global H3K36me3levels in vivo, disassociates transcription component from the chromatin, triggers the RNAPII ubiquitiation levels, suggesting that SC35might be part of transcriptional machinery and important for its stabilization.