科學家很早以前就知道,，同一基因能夠通過選擇性拼接（Alternative splicing）制造出同一蛋白的不同形態(tài)?，F(xiàn)在,，美國麻省理工學院一個研究小組證明，選擇性拼接的發(fā)生比先前估計的要普遍得多,。相關論文11月2日在線發(fā)表于《自然》（Nature）和《自然—遺傳學》（Nature Genetics）,。
研究人員發(fā)現(xiàn)，大約94%的人類基因會制造出同一蛋白的不同形態(tài),。同一蛋白質(zhì)的不同形態(tài),，會有不同甚至是完全相反的功能。
研究小組從20個人的10種組織和5種細胞系中提取了信使RNA,，生物技術公司Illumina使用新型高通量測序儀器完成了相關測序工作,。
這一結(jié)果為將來研究癌細胞等特定組織中選擇性蛋白的作用鋪平了道路,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature，doi: 10.1038/nature07509,，Eric T. Wang,，Christopher B. Burge
Alternative isoform regulation in human tissue transcriptomes
Eric T. Wang1,2,7, Rickard Sandberg1,3,7, Shujun Luo4, Irina Khrebtukova4, Lu Zhang4, Christine Mayr5, Stephen F. Kingsmore6, Gary P. Schroth4 & Christopher B. Burge1
1 Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
2 Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA
3 Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden
4 Illumina Inc., 25861 Industrial Boulevard, Hayward, California 94545, USA
5 Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
6 National Center for Genome Resources, 2935 Rodeo Park Drive East, Santa Fe, New Mexico 87505, USA
7 These authors contributed equally to this work.
Abstract
Through alternative processing of pre-messenger RNAs, individual mammalian genes often produce multiple mRNA and protein isoforms that may have related, distinct or even opposing functions. Here we report an in-depth analysis of 15 diverse human tissue and cell line transcriptomes on the basis of deep sequencing of complementary DNA fragments, yielding a digital inventory of gene and mRNA isoform expression. Analyses in which sequence reads are mapped to exon–exon junctions indicated that 92–94% of human genes undergo alternative splicing, 86% with a minor isoform frequency of 15% or more. Differences in isoform-specific read densities indicated that most alternative splicing and alternative cleavage and polyadenylation events vary between tissues, whereas variation between individuals was approximately twofold to threefold less common. Extreme or 'switch-like' regulation of splicing between tissues was associated with increased sequence conservation in regulatory regions and with generation of full-length open reading frames. Patterns of alternative splicing and alternative cleavage and polyadenylation were strongly correlated across tissues, suggesting coordinated regulation of these processes, and sequence conservation of a subset of known regulatory motifs in both alternative introns and 3' untranslated regions suggested common involvement of specific factors in tissue-level regulation of both splicing and polyadenylation.
Nature Genetics，doi: 10.1038/ng.259,，Qun Pan,，Benjamin J Blencowe
Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing
Qun Pan1, Ofer Shai1,2, Leo J Lee1,2, Brendan J Frey1,2 & Benjamin J Blencowe1,3
We carried out the first analysis of alternative splicing complexity in human tissues using mRNA-Seq data. New splice junctions were detected in 20% of multiexon genes, many of which are tissue specific. By combining mRNA-Seq and EST-cDNA sequence data, we estimate that transcripts from 95% of multiexon genes undergo alternative splicing and that there are 100,000 intermediate- to high-abundance alternative splicing events in major human tissues. From a comparison with quantitative alternative splicing microarray profiling data, we also show that mRNA-Seq data provide reliable measurements for exon inclusion levels.
1 Banting and Best Department of Medical Research, University of Toronto, Toronto M5S 3E1, Canada.
2 Department of Electrical and Computer Engineering, University of Toronto, Toronto M5S 3G4, Canada.
3 Department of Molecular Genetics, University of Toronto, Toronto M5S 3E1, Canada.
