The mRNP-Code: Regulation of Maturation, Transport, Stability and Translation of mRNA-containing Ribonucleoproteins

Organizers: Thomas Tuschl and Markus Landthaler, The Rockefeller University

Speakers: Jens Lykke-Andersen, University of Colorado; Georg Stoecklin, German Cancer Research Center; Carolyn J. Decker, Howard Hughes Medical Institute; Edward Chan, University of Florida; Marianthi Kiriakidou, University of Pennsylvania; Shobha Vasudevan, Yale University School of Medicine; Markus Landthaler, Rockefeller University; Pam Silver, Harvard University; Scott Tenebaum, SUNY at Albany; Matteo Ruggiu, Rockefeller University

Session I: RNA Stability

9:15-9:55 AM:
Robert Singer

9:55-10:35 AM: mRNA Turnover In Regulation of Human Gene Expression
Jens Lykke-Andersen

10:35-11:00 AM: Coffee Break

11:00-11:35 AM: Recognition and Regulation of mRNAs Containing AU-rich Elements by Tristetraprolin
Georg Stoecklin

11:30-12:05 PM: Redundant and Specific Mechanisms for P-body Assembly in Saccharomyces cerevisiae
Carolyn J. Decker

12:05-1:00 PM: Lunch

Session II: RNA interference

1:00-1:40 PM: Cytoplasmic Foci GW Bodies are Markers for RNA Interference Activity
Edward Chan

1:40-2:20 PM
Marianthi Kiriakidou

2:20-2:50 PM:
Shobha Vasudevan

2:50-3:20 PM: Characterization of human Argonaute protein-containing RNP complexes and associated mRNAs
Markus Landthaler

3:20-3:50 PM: Coffee Break

Session III: RNA Systems Biology

3:50-4:30 PM: Connecting the Genome to the Cytoplasm
Pam Silver

4:30-5:10 PM: Using RNA-binding Proteins and miRNAs for the Genomic-scale Identification of Regulatory Elements in RNA
Scott Tenenbaum

5:10-5:45 PM: Alternative splicing and the synapse: the splicing factor NOVA regulates the formation of the neuromuscular junction
Matteo Ruggiu

5:45-7:00 PM: Reception

Abstracts

mRNA Turnover In Regulation of Human Gene Expression
Jens Lykke-Andersen
University of Colorado

mRNA turnover plays an essential role in gene expression. Specific cell signals can transiently stabilize unstable mRNAs or destabilize stable mRNAs to regulate protein expression. Mis-regulation of mRNA decay is associated with a range of human diseases. Two important mRNA decay processes that we study are those of nonsense-mediated decay (NMD), a process that detects and degrades aberrant mRNAs that fail to encode full-length protein, and AU-rich element (ARE)-mediated decay, which is responsible for the rapid decay of mRNAs with AREs. AREs are found in the 3'UTR of many mRNAs encoding proto-oncogenes, cytokines and growth factors. Both of these mRNA decay pathways trigger rapid mRNA dedadenylation and decapping, two important, often regulatory steps in mRNA decay. Recent evidence has shown that a number of proteins involved in translational silencing and mRNA decay localize in sub-cytoplasmic foci called processing bodies (PBs). With the long-term goal of understanding how mRNA decay is regulated in human gene expression, we have recently focused on the connection between PBs and the NMD and ARE-mRNA decay pathways. Our recent observations suggest that PBs function as "reservoirs" for mRNAs that are targeted for decay, but whose degradation have been delayed. This sequesters the mRNAs away from the translational machinery and therefore shuts off mRNA function even before its decay. PBs therefore appear to function as a "buffer" for the cellular mRNA decay machinery, ensuring that even under conditions where the mRNA decay machinery is overwhelmed, targeted mRNAs are kept silent.

Recognition and Regulation of mRNAs Containing AU-rich Elements by Tristetraprolin
Georg Stoecklin, MD, PhD
German Cancer Research Center

The RNA-binding protein tristetraprolin (TTP) is required for the rapid degradation of a class of mRNAs that contain an AU-rich element (ARE) in their 3' untranslated region. In macrophages, TTP serves to dampen the expression of cytokines such as TNFα and GM-CSF by destabilizing their mRNAs. Upon macrophage activ