October 2011

The seven wonders of the RNA world


Meetings_RNARight in the middle of the central dogma sits the RNA world, through which the information in DNA passes to create the functional state of the cell. This world is rife with nonprotein enzymes, mystery machines and unfathomed regulatory sophistication. Among its wonders are the ribosome, the spliceosome, catalytic RNAs, small transregulatory RNAs such as microRNAs and CRISPRs, large noncoding RNAs, riboswitches and RNA helicases. In the annual meeting thematic group “RNA: from Catalysis to Regulation,” we will explore the surface of this world in four parts.

The elusive spliceosome 

Eukaryotic genes are split such that the interpretation of what information should go into the mRNA is left to the spliceosome, a bevy of complexes that bind, arrange and splice exons together. The coordinated transitions from one complex to the next are so dynamic that structural analysis requires tricks to freeze the spliceosome in its tracks.

The first session, “The Spliceosome: Fitting the Pieces Together,” will focus on this mystery. First up will be Soo-Chen Cheng (Academia Sinica in Taipei), who will relate spliceosome dynamics to function in either of the two reversible catalytic steps carried out by the yeast spliceosome.

How spliceosome function is influenced by the ongoing transcription that creates its substrate will be addressed by Tracy L. Johnson (University of California, San Diego), who will describe studies of co-transcriptional splicing and spliceosome dynamics.

Finally, Melissa S. Jurica (University of California, Santa Cruz) will describe key changes in protein composition and complex structure that accompany human spliceosome transitions in vitro.

Fate as a matter of folding

Some rules for RNA folding are simple: G pairs with C or U, and A pairs with U. These rules (plus stacking) generate an RNA-folding landscape that can include many stable solutions. The next layer is more obscure, with tertiary interactions and helical packing interactions that create the functional shape.

The second session, “RNA Dynamics: Function Follows Folding,” will explore how these interactions affect the function of RNA elements.

Manny Ares (University of California, Santa Cruz) will describe a riboswitchlike pre-mRNA structure that folds differently under the influence of polyamines to regulate alternative splicing.

Most dynamic RNAs are aided by proteins that remodel RNA structure. This topic will be presented by Eckhard Jankowsky (Case Western Reserve University), who will describe in molecular terms how the RNA helicase family of enzymes works and how this explains their physiological roles.

Finally, the complex shape and function of a folded catalytic RNA will be dissected by Anna M. Pyle (Yale University), who will discuss group II intron architecture and its implications for the development of eukaryotic splicing systems.

Fighting fire with fire: RNA control of gene function 

Accurate molecular recognition is fundamental to correct regulation, and evolution has partly solved this problem by targeting RNA with RNA.

In the third session, “RNA-based Regulation: A Diversity of Mechanisms,” we will hear about how RNAs that mediate regulation are made and how they function. Among the speakers will be Richard Gregory (Harvard University), who has focused on the biogenesis of microRNAs that control stem-cell function and are affected in cancer cells.

In a still-breaking story, bacteria appear to have immunity systems that utilize RNA recognition. Rebecca M. Terns (University of Georgia) will explain how small RNAs from CRISPR loci guide silencing of invaders in prokaryotes.

Lynne Maquat (University of Rochester) will describe how RNA decay plays a central role in the ability of RNAs to keep their regulatory targets in check.



Delivering the message 

Qualitative and quantitative protein output is the ultimate hallmark of cell function. Key mechanisms to control this are focused at two points: initiation of translation when the mRNA encounters the ribosome and a still-enigmatic step controlled by microRNAs. In the final session, “Ribosomes: Regulation of Access to mRNA,” we will explore these key steps.

First, Tatyana Pestova (State University of New York Downstate Medical Center) will present her work on the mechanisms of initiation of prokaryotic protein synthesis.

Although prokaryotic ribosomes have informed our understanding of eukaryotic translation, there remain important differences. Jon Lorsch (Johns Hopkins University School of Medicine) will explain how the mechanics of mRNA recruitment to the eukaryotic ribosome leads to control of initiation.

Finally, Nahum Sonenberg (McGill University) will treat us to his lab’s latest findings on the mechanism of action of miRNAs in controlling mRNA translation.

Meetings_RNA_MANNY_ARESMeetings_RNA_Tracy_JohnsonManny Ares (ares@biology.ucsc.edu)  is a professor at the University of California, Santa Cruz, and Tracy Johnson (johnsont@ucsd.edu) is an associate professor at the University of California, San Diego. 

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