PTBP1 and PTBP2 Repress Nonconserved Cryptic Exons

被引:44
作者
Ling, Jonathan P. [1 ]
Chhabra, Resham [1 ]
Merran, Jonathan D. [2 ]
Schaughency, Paul M. [3 ]
Wheelan, Sarah J. [2 ,4 ]
Corden, Jeffry L. [2 ]
Wong, Philip C. [1 ,5 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA
[5] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA
来源
CELL REPORTS | 2016年 / 17卷 / 01期
关键词
TRACT-BINDING-PROTEIN; GENOME-WIDE ANALYSIS; NEURONAL REGULATION; EXPRESSION ANALYSIS; SPLICING REGULATION; PYRUVATE-KINASE; HNRNP PROTEINS; IN-VIVO; RNA; BRAIN;
D O I
10.1016/j.celrep.2016.08.071
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The fidelity of RNA splicing is maintained by a network of factors, but the molecular mechanisms that govern this process have yet to be fully elucidated. We previously found that TDP-43, an RNA-binding protein implicated in neurodegenerative disease, utilizes UG microsatellites to repress nonconserved cryptic exons and prevent their incorporation into mRNA. Here, we report that two well-characterized splicing factors, polypyrimidine tract-binding protein 1 (PTBP1) and polypyrimidine tract-binding protein 2 (PTBP2), are also nonconserved cryptic exon repressors. In contrast to TDP-43, PTBP1 and PTBP2 utilize CU microsatellites to repress both conserved tissue-specific exons and nonconserved cryptic exons. Analysis of these conserved splicing events suggests that PTBP1 and PTBP2 repression is titrated to generate the transcriptome diversity required for neuronal differentiation. We establish that PTBP1 and PTBP2 are members of a family of cryptic exon repressors.
引用
收藏
页码:104 / 113
页数:10
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