科学家很早以前就知道，同一基因能够通过选择性拼接（Alternative splicing）制造出同一蛋白的不同形态。现在，美国麻省理工学院一个研究小组证明，选择性拼接的发生比先前估计的要普遍得多。相关论文11月2日在线发表于《自然》（Nature）和《自然—遗传学》（Nature Genetics）。
研究人员发现，大约94%的人类基因会制造出同一蛋白的不同形态。同一蛋白质的不同形态，会有不同甚至是完全相反的功能。
研究小组从20个人的10种组织和5种细胞系中提取了信使RNA，生物技术公司Illumina使用新型高通量测序仪器完成了相关测序工作。
这一结果为将来研究癌细胞等特定组织中选择性蛋白的作用铺平了道路。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
