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Deep sequencing of mRNA to understand function of splicing regulatory factors
Author(s) -
Burge Chris
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.422.3
Subject(s) - rna splicing , alternative splicing , exon , splicing factor , exonic splicing enhancer , splice , enhancer , biology , gene knockdown , computational biology , genetics , intron , gene , gene expression , rna
Splicing regulatory elements (SREs) and the associated splicing factors play central roles in the control of pre‐mRNA splicing and in exon evolution. We are studying in depth the regulatory properties of representative splicing factors, including the widely expressed factor hnRNP H, and the muscle‐ and brain‐specific factors of the CELF and Muscleblind families, using knockout or knockdown followed by deep sequencing of mRNAs (KO‐Seq or KD‐Seq), cross‐linking/immunoprecipitation/sequencing (CLIP‐Seq), and other approaches. In this talk I will discuss our progress towards understanding the functions of these factors, including the finding that the activity of G‐run intronic splicing enhancers (ISEs) and hnRNP H is highly dependent on the strength of the adjacent 5' splice site sequence, and the functional and evolutionary implications of this finding. Our work is supported by the NHGRI and the NIGMS.