Translational regulation by short RNAs in mammalian cells

The large complexity of animals is thought to depend upon the regulation of gene expression and not the number of genes in a genome. Gene expression is a highly conserved process in which genes encoded by DNA are transcribed in the nucleus into messenger RNA, spliced, and exported to the cytoplasm, where they are translated into proteins. It was therefore a profound surprise when RNA itself, in the form of [approx.]21nt short RNAs, was discovered to have major generalized roles in the regulation of mRNAs which are typically 100 times larger in size. These short RNAs, siRNAs and microRNAs, exert their influence on gene expression in mammals by RNA interference (RNAi) and translational repression. RNAi initiated by exogenous siRNAs results in mRNA degradation whereas many endogenous microRNAs cause translational repression. Some factors which produce siRNAs from double-stranded RNA or microRNAs from hairpin precursors are shared and some are unique to each pathway. Our work shows the interaction between short RNA and target mRNA, not the origin of the short RNA, dictates the outcome of silencing. Perfectly or nearly perfectly complementary basepairing between short RNA and target mRNA causes RNAi-mediated degradation of the mRNA, whereas partial basepairing results in translational repression and a degree of mRNA degradation.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Petersen, Christian Paul

Advisor dc:contributor.advisor

• Phillip A. Sharp.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/34190
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/34190

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/34190