Harvard University - Department of Molecular & Cellular Biology

"VICTORIA D'SOUZA: "UNRAVELING VIRAL RNA GENOMES: ONE SEGMENT AT A TIME" (MCB)

Date/Time Thu, 11/21/2013, noon – 1 p.m.
Location NW Lecture Hall B-103 (52 Oxford St.)
Description "Unraveling viral RNA genomes: One segment at a time"

Victoria D'Souza, Ph.D.
Associate Professor of Molecular and Cellular Biology
Harvard University

Abstract:
Viruses that use RNA as their genetic material have evolved unique strategies to manipulate their host cells. The genomic RNA forms structurally organized domains that play a critical role during various stages of the viral life cycle. My talk will focus on three such events: (#1) retroviral primer annealing, which is required to initiate reverse transcription, (#2) regulation of transcriptional elongation and (#3) genetic recoding during protein translation.

(#1) Retroviruses require annealing of a specific tRNA molecule to the viral genome in order to prime reverse transcription. The residues essential for primer annealing are initially locked in intramolecular interactions, and hence, annealing requires the retroviral nucleocapsid protein (a chaperone) to facilitate structural rearrangements. My talk will describe a novel capture-and-release model for retroviral primer annealing and provide mechanistic insight as to how ATP-independent chaperones can recognize and destabilize specific RNA targets.

(#2) The transition from transcriptional initiation to elongation of the integrated HIV-1 genome is critical for expression of the complete viral mRNA, and is achieved via recruitment of positive transcriptional elongation factor P-TEFb to the paused transcriptional complex. The viral Tat protein plays a central role in this process by interacting with cellular small nuclear 7SK ribonucleoprotein, which sequesters the essential P-TEFb. My talk will detail the structural properties of the interaction between Tat and 7SK, and will highlight the molecular mimicry that takes place between the cellular and viral components, which ultimately allows for the switch between paused to elongating transcriptional complex.

(#3) Genetic recodingeither by ribosomal frameshifting or stop codon read-throughis critical for replication of diverse viruses. It ensures the production of correct viral protein ratios from a bicistronic mRNA message during translation. A major question in the field is to understand how the frequency of recoding is maintained; that is, why do only a subset of ribosomes recode after encountering the recoding signal on the mRNA. I will describe a structure-based equilibrium mechanism that explains this frequency maintenance.
  (Molecular & Cellular Biology)
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