Identification of two short peptide motifs from serine/arginine-rich protein ribonucleic acid recognition motif-1 domain acting as splicing regulators
Background Serine/arginine-rich (SR) proteins regulate pre-mRNA splicing. However, structurally similar proteins often behave differently in splicing regulation and the underlying mechanisms are largely unknown. Here, using SMN1/2 minigenes we extensively analyzed four SR proteins, SRSF1/5/6/9. Meth...
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PeerJ Inc.
2023-09-01
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| Online Access: | https://peerj.com/articles/16103.pdf |
| _version_ | 1797419830958096384 |
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| author | Tao Jiang Li Wang Liang Tang Azhar Zeb Yanjun Hou |
| author_facet | Tao Jiang Li Wang Liang Tang Azhar Zeb Yanjun Hou |
| author_sort | Tao Jiang |
| collection | DOAJ |
| description | Background Serine/arginine-rich (SR) proteins regulate pre-mRNA splicing. However, structurally similar proteins often behave differently in splicing regulation and the underlying mechanisms are largely unknown. Here, using SMN1/2 minigenes we extensively analyzed four SR proteins, SRSF1/5/6/9. Methods In this study, the effects of these proteins on SMN1/2 exon 7 splicing when tethered at either intron 6 or 7 were evaluated using an MS2-tethering assay. Deletion analysis in four SR proteins and co-overexpression analysis were performed. Results Splicing outcomes varied among all four SR proteins, SRSF1 and SRSF5 function the same at the two sites, acting as repressor and stimulator, respectively; while SRSF6 and SRSF9 promote exon 7 inclusion at only one site. Further, the key domains of each SR proteins were investigated, which identified a potent inhibitory nonapeptide in the C-terminus of SRSF1/9 ribonucleic acid recognition motif-1 (RRM1) and a potent stimulatory heptapeptide at the N-terminus of SRSF5/6 RRM1. Conclusion The insight of the four SR proteins and their domains in affecting SMN gene splicing brings a new perspective on the modes of action of SR proteins; and the functional peptides obtained here offers new ideas for developing splice switching-related therapies. |
| first_indexed | 2024-03-09T06:53:57Z |
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| id | doaj.art-2b5f59ec45a3406cbb4fcb773ab69b27 |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:53:57Z |
| publishDate | 2023-09-01 |
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| spelling | doaj.art-2b5f59ec45a3406cbb4fcb773ab69b272023-12-03T10:12:50ZengPeerJ Inc.PeerJ2167-83592023-09-0111e1610310.7717/peerj.16103Identification of two short peptide motifs from serine/arginine-rich protein ribonucleic acid recognition motif-1 domain acting as splicing regulatorsTao Jiang0Li Wang1Liang Tang2Azhar Zeb3Yanjun Hou4Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, NanJing, ChinaJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, NanJing, ChinaJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, NanJing, ChinaJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, NanJing, ChinaJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, NanJing, ChinaBackground Serine/arginine-rich (SR) proteins regulate pre-mRNA splicing. However, structurally similar proteins often behave differently in splicing regulation and the underlying mechanisms are largely unknown. Here, using SMN1/2 minigenes we extensively analyzed four SR proteins, SRSF1/5/6/9. Methods In this study, the effects of these proteins on SMN1/2 exon 7 splicing when tethered at either intron 6 or 7 were evaluated using an MS2-tethering assay. Deletion analysis in four SR proteins and co-overexpression analysis were performed. Results Splicing outcomes varied among all four SR proteins, SRSF1 and SRSF5 function the same at the two sites, acting as repressor and stimulator, respectively; while SRSF6 and SRSF9 promote exon 7 inclusion at only one site. Further, the key domains of each SR proteins were investigated, which identified a potent inhibitory nonapeptide in the C-terminus of SRSF1/9 ribonucleic acid recognition motif-1 (RRM1) and a potent stimulatory heptapeptide at the N-terminus of SRSF5/6 RRM1. Conclusion The insight of the four SR proteins and their domains in affecting SMN gene splicing brings a new perspective on the modes of action of SR proteins; and the functional peptides obtained here offers new ideas for developing splice switching-related therapies.https://peerj.com/articles/16103.pdfSR proteinPre-mRNA splicingSMN1/2RRMShort peptide motifs |
| spellingShingle | Tao Jiang Li Wang Liang Tang Azhar Zeb Yanjun Hou Identification of two short peptide motifs from serine/arginine-rich protein ribonucleic acid recognition motif-1 domain acting as splicing regulators PeerJ SR protein Pre-mRNA splicing SMN1/2 RRM Short peptide motifs |
| title | Identification of two short peptide motifs from serine/arginine-rich protein ribonucleic acid recognition motif-1 domain acting as splicing regulators |
| title_full | Identification of two short peptide motifs from serine/arginine-rich protein ribonucleic acid recognition motif-1 domain acting as splicing regulators |
| title_fullStr | Identification of two short peptide motifs from serine/arginine-rich protein ribonucleic acid recognition motif-1 domain acting as splicing regulators |
| title_full_unstemmed | Identification of two short peptide motifs from serine/arginine-rich protein ribonucleic acid recognition motif-1 domain acting as splicing regulators |
| title_short | Identification of two short peptide motifs from serine/arginine-rich protein ribonucleic acid recognition motif-1 domain acting as splicing regulators |
| title_sort | identification of two short peptide motifs from serine arginine rich protein ribonucleic acid recognition motif 1 domain acting as splicing regulators |
| topic | SR protein Pre-mRNA splicing SMN1/2 RRM Short peptide motifs |
| url | https://peerj.com/articles/16103.pdf |
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