How prevalent is functional alternative splicing in the human genome?

被引:233
作者
Sorek, R
Shamir, R
Ast, G [1 ]
机构
[1] Tel Aviv Univ, Sackler Fac Med, Dept Human Genet, IL-69978 Ramat Aviv, Israel
[2] Compugen, IL-69512 Tel Aviv, Israel
[3] Tel Aviv Univ, Sch Comp Sci, IL-69978 Tel Aviv, Israel
关键词
D O I
10.1016/j.tig.2003.12.004
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Comparative analyses of ESTs and cDNAs with genomic DNA predict a high frequency of alternative splicing in human genes. However, there is an ongoing debate as to how many of these predicted splice variants are functional and how many are the result of aberrant splicing (or 'noise'). To address this question, we compared alternatively spliced cassette exons that are conserved between human and mouse with EST-predicted cassette exons that are not conserved in the mouse genome. Presumably, conserved exon-skipping events represent functional alternative splicing. We show that conserved (functional) cassette exons possess unique characteristics in size, repeat content and in their influence on the protein. By contrast, most non-conserved cassette exons do not share these characteristics. We conclude that a significant portion of cassette exons evident in EST databases is not functional, and might result from aberrant rather than regulated splicing.
引用
收藏
页码:68 / 71
页数:4
相关论文
共 21 条
[1]   In silico screening for tumour-specific expressed sequences in human genome [J].
Baranova, AV ;
Lobashev, AV ;
Ivanova, DV ;
Krukovskaya, LL ;
Yankovsky, NK ;
Kozlov, AP .
FEBS LETTERS, 2001, 508 (01) :143-148
[2]   Intron-exon structures of eukaryotic model organisms [J].
Deutsch, M ;
Long, M .
NUCLEIC ACIDS RESEARCH, 1999, 27 (15) :3219-3228
[3]   Alternative splicing: increasing diversity in the proteomic world [J].
Graveley, BR .
TRENDS IN GENETICS, 2001, 17 (02) :100-107
[4]   Selecting for functional alternative splices in ESTs [J].
Kan, ZY ;
States, D ;
Gish, W .
GENOME RESEARCH, 2002, 12 (12) :1837-1845
[5]   Evolution of alternative splicing: deletions, insertions and origin of functional parts of proteins from intron sequences [J].
Kondrashov, FA ;
Koonin, EV .
TRENDS IN GENETICS, 2003, 19 (03) :115-119
[6]   Editing of glutamate receptor B subunit ion channel RNAs by four alternatively spliced DRADA2 double-stranded RNA adenosine deaminases [J].
Lai, F ;
Chen, CX ;
Carter, KC ;
Nishikura, K .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (05) :2413-2424
[7]   Initial sequencing and analysis of the human genome [J].
Lander, ES ;
Int Human Genome Sequencing Consortium ;
Linton, LM ;
Birren, B ;
Nusbaum, C ;
Zody, MC ;
Baldwin, J ;
Devon, K ;
Dewar, K ;
Doyle, M ;
FitzHugh, W ;
Funke, R ;
Gage, D ;
Harris, K ;
Heaford, A ;
Howland, J ;
Kann, L ;
Lehoczky, J ;
LeVine, R ;
McEwan, P ;
McKernan, K ;
Meldrim, J ;
Mesirov, JP ;
Miranda, C ;
Morris, W ;
Naylor, J ;
Raymond, C ;
Rosetti, M ;
Santos, R ;
Sheridan, A ;
Sougnez, C ;
Stange-Thomann, N ;
Stojanovic, N ;
Subramanian, A ;
Wyman, D ;
Rogers, J ;
Sulston, J ;
Ainscough, R ;
Beck, S ;
Bentley, D ;
Burton, J ;
Clee, C ;
Carter, N ;
Coulson, A ;
Deadman, R ;
Deloukas, P ;
Dunham, A ;
Dunham, I ;
Durbin, R ;
French, L .
NATURE, 2001, 409 (6822) :860-921
[8]   The birth of an alternatively spliced exon:: 3′ splice-site selection in Alu exons [J].
Lev-Maor, G ;
Sorek, R ;
Shomron, N ;
Ast, G .
SCIENCE, 2003, 300 (5623) :1288-1291
[9]  
MAKALOWSKI W, 2003, GENOMICS, V300, P1246
[10]   Alternative pre-mRNA splicing and proteome expansion in metazoans [J].
Maniatis, T ;
Tasic, B .
NATURE, 2002, 418 (6894) :236-243