Suppression of 5′ splice-sites through multiple exonic motifs by hnRNP L
| Autor: | Jianhua Zhou, Namjeong Choi, Heegyum Moon, Haihong Shen, Xuexiu Zheng, Tiing Jen Loh, Yongchao Liu, Ha Na Jang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
RNA Splicing Kruppel-Like Transcription Factors Biophysics Exonic splicing enhancer Biology environment and public health Biochemistry 03 medical and health sciences Exon Structural Biology Cell Line Tumor Proto-Oncogene Proteins Kruppel-Like Factor 6 RNA Precursors Genetics Humans splice Nucleotide Motifs Molecular Biology Heterogeneous-Nuclear Ribonucleoprotein L Regulation of gene expression Serine-Arginine Splicing Factors Alternative splicing Exons 030104 developmental biology KLF6 Ribonucleoproteins RNA splicing RNA Splice Sites |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1860:363-373 |
| ISSN: | 1874-9399 |
| Popis: | Selection of 5' splice-sites (5'SS) in alternative splicing plays an important role in gene regulation. Although regulatory mechanisms of heterogeneous nuclear ribonucleoprotein L (hnRNP L), a well-known splicing regulatory protein, have been studied in a substantial level, its role in 5'SS selection is not thoroughly defined. By using a KLF6 pre-mRNA alternative splicing model, we demonstrate in this report that hnRNP L inhibits proximal 5'SS but promotes two consecutive distal 5'SS splicing, antagonizing SRSF1 roles in KLF6 pre-mRNA splicing. In addition, three consecutive CA-rich sequences in a CA cassette immediately upstream of the proximal 5'SS are all required for hnRNP L functions. Importantly, the CA-cassette locations on the proximal exon do not affect hnRNP L roles. We further show that the proximal 5'SS but not the two distal 5'SSs are essential for hnRNP L activities. Notably, in a Bcl-x pre-mRNA model that contains two alternative 5'SS but includes CA-rich elements at distal exon, we demonstrate that hnRNP L also suppresses nearby 5'SS activation. Taken together, we conclude that hnRNP L suppresses 5'SS selection through multiple exonic motifs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect