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Suppression of 5' splice-sites through multiple exonic motifs by hnRNP L.
Biochim Biophys Acta Gene Regul Mech. 2017 Mar; 1860(3):363-373.BB

Abstract

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.

Authors+Show Affiliations

School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea. Electronic address: xuexiuzheng@gist.ac.kr.School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea. Electronic address: haihongshen@gist.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28119102

Citation

Loh, Tiing Jen, et al. "Suppression of 5' Splice-sites Through Multiple Exonic Motifs By hnRNP L." Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms, vol. 1860, no. 3, 2017, pp. 363-373.
Loh TJ, Choi N, Moon H, et al. Suppression of 5' splice-sites through multiple exonic motifs by hnRNP L. Biochim Biophys Acta Gene Regul Mech. 2017;1860(3):363-373.
Loh, T. J., Choi, N., Moon, H., Jang, H. N., Liu, Y., Zhou, J., Zheng, X., & Shen, H. (2017). Suppression of 5' splice-sites through multiple exonic motifs by hnRNP L. Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms, 1860(3), 363-373. https://doi.org/10.1016/j.bbagrm.2017.01.010
Loh TJ, et al. Suppression of 5' Splice-sites Through Multiple Exonic Motifs By hnRNP L. Biochim Biophys Acta Gene Regul Mech. 2017;1860(3):363-373. PubMed PMID: 28119102.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Suppression of 5' splice-sites through multiple exonic motifs by hnRNP L. AU - Loh,Tiing Jen, AU - Choi,Namjeong, AU - Moon,Heegyum, AU - Jang,Ha Na, AU - Liu,Yongchao, AU - Zhou,Jianhua, AU - Zheng,Xuexiu, AU - Shen,Haihong, Y1 - 2017/01/22/ PY - 2016/09/20/received PY - 2017/01/20/revised PY - 2017/01/20/accepted PY - 2017/1/26/pubmed PY - 2017/8/15/medline PY - 2017/1/26/entrez KW - 5′ splice-site selection KW - KLF6 KW - Pre-mRNA splicing KW - hnRNP L SP - 363 EP - 373 JF - Biochimica et biophysica acta. Gene regulatory mechanisms JO - Biochim Biophys Acta Gene Regul Mech VL - 1860 IS - 3 N2 - 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. SN - 1874-9399 UR - https://www.unboundmedicine.com/medline/citation/28119102/Suppression_of_5'_splice_sites_through_multiple_exonic_motifs_by_hnRNP_L_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1874-9399(17)30030-5 DB - PRIME DP - Unbound Medicine ER -