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SRSF1-3, a splicing and somatic hypermutation regulator, controls transcription of IgV genes via chromatin regulators SATB2, UBN1 and histone variant H3.3.
- Source :
-
Molecular Immunology . Mar2020, Vol. 119, p69-82. 14p. - Publication Year :
- 2020
-
Abstract
- • RNASeq analysis of SRSF1–3 reconstituted cells shows upregulation of SATB2 and UBN1. • Increased SATB2 and UBN1 are enriched in the MAR and promoter regions of IgL gene. • Enhanced occupancy of UBN1, histone H3.3 & SATB2 leads to increased IgL transcription. • Splicing isoform SRSF1–3 regulates alternate splicing pattern of many genes. SRSF1, a member of the SR protein family, is an important splicing factor and regulator of splicing. Multiple splicing isoforms have been reported for this gene. SRSF1–3, a splicing isoform of SRSF1, is necessary for AID-dependent SHM of Ig V genes. However, its precise role in SHM remains enigmatic. Transcriptomic analysis of SRSF1–3 reconstituted cells shows upregulation of transcription factor SATB2 and chromatin regulator UBN1. The increased SATB2 and UBN1 are strikingly enriched in the MAR and promoter regions of the Ig L gene, respectively. Furthermore, UBN1 enrichment at the promoter region was coupled with a hundred-fold enhanced occupancy of the histone variant H3.3 at the Ig L promoter, that is a hallmark of efficient SHM. The enhanced occupancy of SATB2 at the MAR, UBN1 and histone variant H3.3 at the Ig L promoter leads to an increase in Ig L transcription, revealing a role of SRSF1–3 in SHM. Thus, SRSF1–3 is likely involved in the regulation of SHM, via upregulation of a crucial transcription factor SATB2, as well as, by overexpression of a chromatin modulator of Ig genes, UBN1, which further assists in the recruitment of the histone variant H3.3. Furthermore, the splicing isoform SRSF1–3 regulates alternate splicing pattern of splicing isoforms for various crucial genes. The present study provides the first evidence that a splicing isoform of an SR protein can regulate the post-transcriptional processing of RNA in vivo. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01615890
- Volume :
- 119
- Database :
- Academic Search Index
- Journal :
- Molecular Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 141829761
- Full Text :
- https://doi.org/10.1016/j.molimm.2020.01.005