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Tales from the Cellular Underworld: mRNA Death Dealers

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Uploaded on Jul 22, 2011

Air date: Wednesday, June 01, 2011, 3:00:00 PM
Time displayed is Eastern Time, Washington DC Local
Category: Wednesday Afternoon Lectures
Description: In mammalian cells, two different messenger ribonucleoproteins (mRNPs) serve as templates for protein synthesis. Newly synthesized CBP80-CBP20 (CBC)-bound mRNPs initially undergo a pioneer round of translation (Maquat et al., 2010). One purpose of this round of translation is to ensure the quality of gene expression, as exemplified by nonsense-mediated mRNA decay (NMD). NMD largely functions to eliminate mRNAs that prematurely terminate translation, although NMD also contributes to proper gene control, and it targets CBC-bound mRNPs (for recent publications, see Sato et al., 2008; Isken et al., 2008). CBC-bound mRNPs are remodeled to eIF4E-bound mRNPs as a consequence of the pioneer round of translation as well as independently of translation, e.g., by importin-b binding to importin-a-associated CBC (Sato and Maquat, 2009). eIF4E-bound mRNPs support the bulk of cellular protein synthesis and are the primary targets of mRNA decay mechanisms that conditionally regulate gene expression, such as Staufen1-mediated mRNA decay (see, e.g., Gong et al., 2009).

Mechanistic aspects of NMD will be discussed, including how CBP80, which is acquired by the 5' caps of newly synthesized transcripts within nuclei, promotes NMD at multiple steps by promoting specific mRNP rearrangements (Hwang et al., 2010). Mechanistic aspects of SMD will also be described, including the formation of Staufen1-binding sites not only by intramolecular base-pairing within an mRNA 3'-untranslated region but also by intermolecular base-pairing between the Alu element of an mRNA 3-untranslated region and a partially complementary Alu element within a long noncoding RNA (Gong and Maquat, 2011). These are new functions for Alu elements and for long noncoding RNAs, which we call 1/2-sbsRNAs.

The NIH Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide.

For more information, visit:
The NIH Director's Wednesday Afternoon Lecture Series
Author: Dr. Lynne Maquat, University of Rochester Center for RNA Biology
Runtime: 00:44:37
Permanent link: http://videocast.nih.gov/launch.asp?1...

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