Max-planck-gesellschaft Zur F&#xf6;rderung Der Wissenschaften E. V.

Massachusetts Institute of Technology

University of Massachusetts

Whitehead Institute for Biomedical Research

Whitehead Institute of Biomedical Technology

Europaisches Laboratorium Fur Molekularbiologie

Winfried Lendeckel

Thomas Tuschl

Sayda Mahgoub Elbashir

Reinhard Rauhut

Mariana Lagos-Quintana

Jutta Meyer

Reinhard Luehrmann

Matthias Wilm

Jutta Dammann

Reinhard Lührmann

Sayda Elbashir

Marina Lagos-Quintana

Reinhard Luhrmann

Reinhard LÜHRMANN

Double-stranded RNA (dsRNA) induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi). Using ain vitro system, we demonstrate that 19-23 nt short 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 produced siRNP complex.

RNA interference mediating small RNA molecules

In, lin-4 and let-7 enclode 22- and 21-nucleotide RNAs, respectively, that function as key regulators of developmental timing. Because the appearance of these short RNAs is regulated during development, they are also referred to as 'small temporal RNAs' (stRNAs). We show that many more 21- and 22-nt expressed RNAs, termed microRNAs, (miRNAs), exist in invertebrates and vertebrates, and that some of these novel RNAs, similar to let-7 stRAN, are also highly conserved. This suggests that sequence-specific post-transcriptional regulatory mechanisms mediated by small RNAs are more general than previously appreciated.

Identification of novel genes coding for small temporal RNAs

In, lin-4 and let-7 encode 22- and 21-nucleotide RNAs, respectively, that function as key regulators of developmental timing. Because the appearance of these short RNAs is regulated during development, they are also referred to as 'small temporal RNAs' (stRNAs). We show that many more 21- and 22-nt expressed RNAs, termed microRNAs, (miRNAs), exist in invertebrates and vertebrates, and that some of these novel RNAs, similar to let-7 stRAN, are also highly conserved. This suggests that sequence-specific post-transcriptional regulatory mechanisms mediated by small RNAs are more general than previously appreciated.

Double-stranded RNA (dsRNA) induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi). Using ain vitro system, we demonstrate that 19-23 nt short 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 produced siRNP complex.

Growing community of inventors

Hohengandern, Germany

Winfried Lendeckel