J. Robert Hogg, PhD, National Heart, Lung, and Blood Institute/NIH

A major focus of the lab is to study how the nonsense-mediated mRNA decay pathway recognizes and degrades transcripts containing stop codons at sites distant from the poly(A) tail (i.e. mRNAs with long 3’ UTRs). Using PP7CP-based affinity purification of endogenously assembled mRNPs, Dr. Hogg has demonstrated that the key nonsense-mediated decay factor Upf1 associates with mRNAs in a 3’ UTR length-dependent manner. His findings have led to the development of a model for mRNA quality control surveillance by Upf1 in which non-specific binding of Upf1 to 3’ UTRs allows the protein to sense 3’ UTR length. Enhanced accumulation of Upf1 on long 3’ UTRs would increase the probability that the protein will interact with release factors at a terminating ribosome, a central event in the initiation of mRNA decay. He is currently investigating the regulation of Upf1 association with mRNPs and the molecular events required for the transition between Upf1 binding to mRNPs and the commitment to decay.

In addition to cellular mRNAs, Dr. Hogg is studying the fates of retroviral RNAs. Retroviral transcripts contain elements that allow them to be transcribed at high levels, overcome blocks to nuclear export of unspliced RNAs, be efficiently translated despite significant RNA secondary structure, evade cellular mRNA surveillance machinery, and be efficiently packaged into nascent viral particles. To achieve each of these functions, viral RNAs and proteins collaborate or compete with host cell factors, ensuring efficient viral replication. Despite the central importance of RNP assembly pathways in the biogenesis and activity of viral RNAs, crucial questions remain regarding the mechanisms by which multiple RNAs produced from a single locus can attain very different fates.