RNA interference is mediated by 21- and 22-nucleotide RNAs

Genes and Development - Tập 15 Số 2 - Trang 188-200 - 2001
Sayda M. Elbashir1, Winfried Lendeckel1, Thomas Tuschl1
1Department of Cellular Biochemistry, Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, D-37077 Go ¨ttingen, Germany

Tóm tắt

Double-stranded RNA (dsRNA) induces sequence-specific posttranscriptional gene silencing in many organisms by a process known as RNA interference (RNAi). Using a Drosophila in vitro system, we demonstrate that 21- and 22-nt RNA fragments are the sequence-specific mediators of RNAi. The short interfering RNAs (siRNAs) are generated by an RNase III–like processing reaction from long dsRNA. Chemically synthesized siRNA duplexes with overhanging 3′ ends mediate efficient target RNA cleavage in the lysate, and the cleavage site is located near the center of the region spanned by the guiding siRNA. Furthermore, we provide evidence that the direction of dsRNA processing determines whether sense or antisense target RNA can be cleaved by the siRNA–protein complex.

Từ khóa


Tài liệu tham khảo

10.1126/science.290.5489.142

10.1016/S0092-8674(02)71133-1

10.1038/35000102

10.1016/S0378-1119(00)00224-9

10.1038/35005169

10.1073/pnas.070043997

10.1016/S1357-2725(96)00169-0

10.1016/S1369-5274(99)00041-7

10.1016/S0092-8674(00)80864-8

Dernburg, 2000, Transgene-mediated cosuppression in the C. elegans germ line., Genes & Dev., 14, 1578, 10.1101/gad.14.13.1578

Dunn, 1982, Ribonuclease III., The enzymes, 15, part B, 485, 10.1016/S1874-6047(08)60287-5

10.1016/S0378-1119(99)00571-5

10.1016/S0168-9525(99)01818-1

10.1038/35888

10.1126/science.287.5462.2494

10.1126/science.286.5441.950

10.1038/35005107

Jacobsen, 1999, Disruption of an RNA helicase/RNase III gene in Arabidopsis causes unregulated cell division in floral meristems., Development, 126, 5231, 10.1242/dev.126.23.5231

10.1038/5997

10.1016/S0092-8674(00)81725-0

10.1038/35005113

10.1016/S0092-8674(00)81645-1

10.1093/emboj/19.7.1672

Malinsky, 2000, New insights on homology-dependent silencing of I factor activity by transgenes containing ORF1 in Drosophila melanogaster., Genetics, 156, 1147, 10.1093/genetics/156.3.1147

Matsuda, 2000, Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase., Biochim. Biophys. Acta, 1490, 163, 10.1016/S0167-4781(99)00221-3

10.1016/S0092-8674(00)80863-6

10.1073/pnas.95.25.14687

10.1111/j.1574-6976.1999.tb00405.x

10.1038/35015500

10.1021/bi00131a001

10.1016/S1097-2765(00)00106-4

10.1016/S0959-437X(00)00128-3

10.1105/tpc.11.7.1207

10.1016/0092-8674(82)90270-7

10.1016/0076-6879(90)81121-A

Romaniuk, 1982, The effect of acceptor oligoribonucleotide sequence on the T4 RNA ligase reaction., Eur. J. Biochem., 125, 639, 10.1111/j.1432-1033.1982.tb06730.x

10.1101/gad.13.2.139

10.1002/(SICI)1521-1878(200006)22:6<520::AID-BIES5>3.0.CO;2-W

10.1016/S0960-9822(00)00323-7

Svoboda, 2000, Selective reduction of dormant maternal mRNAs in mouse oocytes by RNA interference., Development, 127, 4147, 10.1242/dev.127.19.4147

10.1016/S0092-8674(00)81644-X

10.1021/bi00094a023

10.1093/emboj/17.9.2637

10.1101/gad.13.24.3191

10.1016/S0092-8674(00)00095-7

10.1038/35000016

Wu, 2000, Human RNase III is a 160 kDa protein involved in preribosomal RNA processing., J. Biol. Chem., 17, 17

10.1016/S0960-9822(00)00732-6

10.1016/S0092-8674(00)80620-0

10.1073/pnas.94.25.13437