生物谷報(bào)道：來(lái)自美國(guó)加州的Douglas Black博士和同事在7月1日的Genes & development期刊上發(fā)表了一篇研究性文章，深入剖析了在神經(jīng)元發(fā)育過(guò)程中可變剪接（alternative splicing）的重新設(shè)定的機(jī)理,。
可變剪接,，指的是通過(guò)剔除其他序列,，將RNA轉(zhuǎn)錄分子剪接成為不同的mRNA分子的過(guò)程。不同類(lèi)型的細(xì)胞在可變剪接上存在著特異性,。
多嘧啶序列結(jié)合蛋白（polypyrimidine tract binding protein,，PTB）是一種可變剪接的抑制分子，可以在多個(gè)細(xì)胞類(lèi)型中起作用,。PTB在神經(jīng)元中的分子,，稱作nPTB。換言之,，nPTB僅僅表達(dá)于神經(jīng)細(xì)胞中,。但是，對(duì)于nPTB的功能,，研究者們一直沒(méi)能闡釋清除,。
現(xiàn)在，Black博士和同事聲稱,，PTB和nPTB的切換,，可引起神經(jīng)元發(fā)育過(guò)程中大量的可變剪接。“PTB蛋白的剪接模式的切換,，決定著有絲分裂后神經(jīng)元的功能情況,。”
原始出處:
GENES & DEVELOPMENT 21:1636-1652, 2007
ISSN 0890-9369/ $5.00
A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons
Paul L. Boutz1,5, Peter Stoilov1,5, Qin Li2, Chia-Ho Lin1, Geetanjali Chawla2, Kristin Ostrow3, Lily Shiue4, Manuel Ares, Jr.4, and Douglas L. Black1,2,6
1 Department of Microbiology, Immunology, and Molecular Genetics, 6-762 MacDonald Research Laboratories, Los Angeles, California 90095, USA; 2 Howard Hughes Medical Institute, 6-762 MacDonald Research Laboratories, Los Angeles, California 90095, USA; 3 Department of Medicine, University of California at San Francisco, San Francisco, California 94143, USA; 4 Sinsheimer Laboratories, Department of Molecular, Cell and Developmental Biology, University of California at Santa Cruz, Santa Cruz, California 95064, USA
Many metazoan gene transcripts exhibit neuron-specific splicing patterns, but the developmental control of these splicing events is poorly understood. We show that the splicing of a large group of exons is reprogrammed during neuronal development by a switch in expression between two highly similar polypyrimidine tract-binding proteins, PTB and nPTB (neural PTB). PTB is a well-studied regulator of alternative splicing, but nPTB is a closely related paralog whose functional relationship to PTB is unknown. In the brain, nPTB protein is specifically expressed in post-mitotic neurons, whereas PTB is restricted to neuronal precursor cells (NPC), glia, and other nonneuronal cells. Interestingly, nPTB mRNA transcripts are found in NPCs and other nonneuronal cells, but in these cells nPTB protein expression is repressed. This repression is due in part to PTB-induced alternative splicing of nPTB mRNA, leading to nonsense-mediated decay (NMD). However, we find that even properly spliced mRNA fails to express nPTB protein when PTB is present, indicating contributions from additional post-transcriptional mechanisms. The PTB-controlled repression of nPTB results in a mutually exclusive pattern of expression in the brain, where the loss of PTB in maturing neurons allows the synthesis of nPTB in these cells. To examine the consequences of this switch, we used splicing-sensitive microarrays to identify different sets of exons regulated by PTB, nPTB, or both proteins. During neuronal differentiation, the splicing of these exon sets is altered as predicted from the observed changes in PTB and nPTB expression. These data show that the post-transcriptional switch from PTB to nPTB controls a widespread alternative splicing program during neuronal development.
[Keywords: Alternative splicing; neuronal development; nonsense-mediated decay; polypyrimidine tract-binding proteins; splicing microarray; ultraconserved element]
Received April 4, 2007; revised version accepted May 16, 2007.
