title: Suppression of 5' splice-sites through multiple exonic motifs by hnRNP L.
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.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Tiing Jen
authors.initials: TJ
authors.lastname: Loh
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Namjeong
authors.initials: N
authors.lastname: Choi
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Heegyum
authors.initials: H
authors.lastname: Moon
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Ha Na
authors.initials: HN
authors.lastname: Jang
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhou
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea. Electronic address: xuexiuzheng@gist.ac.kr.
authors.forename: Xuexiu
authors.initials: X
authors.lastname: Zheng
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea. Electronic address: haihongshen@gist.ac.kr.
authors.forename: Haihong
authors.initials: H
authors.lastname: Shen
mesh_terms: D045744:Cell Line, Tumor; D005091:Exons; D006801:Humans; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D059372:Nucleotide Motifs; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism*; D022821:RNA Splice Sites / Q000502:physiology*; D012326:RNA Splicing / Q000502:physiology*; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors / Q000096:biosynthesis / Q000235:genetics; D034664:Heterogeneous-Nuclear Ribonucleoprotein L
chemical_list: D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D012322:RNA Precursors; D022821:RNA Splice Sites; D012261:Ribonucleoproteins; D000068103:Serine-Arginine Splicing Factors; C400563:HNRNPL protein, human; D034664:Heterogeneous-Nuclear Ribonucleoprotein L; C105465:KLF6 protein, human; C000595779:SRSF1 protein, human
keywords: 5′ splice-site selection; KLF6; Pre-mRNA splicing; hnRNP L