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PTBP1 and PTBP2 Repress Nonconserved Cryptic Exons.

ABSTRACT: 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.

SUBMITTER: Ling JP

PROVIDER: S-EPMC5082185 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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PTBP1 and PTBP2 Repress Nonconserved Cryptic Exons.

Ling Jonathan P JP Chhabra Resham R Merran Jonathan D JD Schaughency Paul M PM Wheelan Sarah J SJ Corden Jeffry L JL Wong Philip C PC

Cell reports 20160901 1

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-bindi ...[more]

PMID: 27681424

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