期刊
CELL CYCLE
卷 15, 期 22, 页码 3026-3032出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2016.1222339
关键词
Neuronal development; RNA-binding proteins; splicing; ribonucleoprotein complex; REST; HNRNPH
类别
资金
- NIA-IRP, NIH [Z01-AG000518-11]
Gene expression patterns change dramatically during neuronal development. Proliferating cells, including neural stem cells (NSCs), express telomere repeat-binding factor 2 (TRF2), a nuclear protein that associates with telomeric proteins, DNA, and RNA telomeres. In NSCs TRF2 also binds to the transcription regulator REST to facilitate repression of numerous neuron-specific genes, thereby keeping the NSCs in a self-renewing state. Upon neuronal differentiation, TRF2 levels decline, REST-regulated neuronal genes are derepressed, and a short isoform of TRF2 arises (TRF2-S) which localizes in the cytoplasm, associates with different subsets of proteins and transcripts, and mobilizes axonal G-rich mRNAs. We recently identified two RNA-binding proteins, HNRNPH1 and H2 (referred to jointly as HNRNPH due to their high homology), which mediate the alternative splicing of an exon required for the expression of full-length TRF2. As HNRNPH levels decline during neurogenesis, TRF2 abundance decreases and TRF2-S accumulates. Here, we discuss the shared and unique functions of TRF2 and TRF2-S, the distinct subcellular compartment in which each isoform resides, the subsets of proteins and nucleic acids with which each interacts, and the functional consequences of these ribonucleoprotein interactions. This paradigm illustrates the dynamic mechanisms through which splicing regulation by factors like HNRNPH enable distinct protein functions as cells adapt to developmental programs such as neurogenesis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据