Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5507702 | Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms | 2017 | 11 Pages |
Abstract
Selection of 5â² splice-sites (5â²SS) 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 5â²SS selection is not thoroughly defined. By using a KLF6 pre-mRNA alternative splicing model, we demonstrate in this report that hnRNP L inhibits proximal 5â²SS but promotes two consecutive distal 5â²SS 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 5â²SS 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 5â²SS but not the two distal 5â²SSs are essential for hnRNP L activities. Notably, in a Bcl-x pre-mRNA model that contains two alternative 5â²SS but includes CA-rich elements at distal exon, we demonstrate that hnRNP L also suppresses nearby 5â²SS activation. Taken together, we conclude that hnRNP L suppresses 5â²SS selection through multiple exonic motifs.
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Authors
Tiing Jen Loh, Namjeong Choi, Heegyum Moon, Ha Na Jang, Yongchao Liu, Jianhua Zhou, Xuexiu Zheng, Haihong Shen,