PTBP1 and PTBP2 Repress Nonconserved Cryptic Exons.
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.
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA.
Jonathan P
JP
Ling
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA.
Resham
R
Chhabra
Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA.
Jonathan D
JD
Merran
Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA.
Paul M
PM
Schaughency
Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA; Department of Biostatistics, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205-2196, USA.
Sarah J
SJ
Wheelan
Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA.
Jeffry L
JL
Corden
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. Electronic address: wong@jhmi.edu.
Philip C
PC
Wong
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D005091:Exons; D006367:HeLa Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D018895:Microsatellite Repeats; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D038941:Polypyrimidine Tract-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009419:Nerve Tissue Proteins; C450006:PTBP1 protein, human; C504334:PTBP2 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D038941:Polypyrimidine Tract-Binding Protein
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