Deepak Koirala, Assistant Professor, Department of Chemistry and Biochemistry, UMBC
Crystal structures of RNA domains that promote viral genome replication and translation
Fri, 18 November, 2022
2:00pm - 3:00pm
Dr. Deepak Koirala, Assistant Professor, Dept. Chemistry and Biochemistry, UMBC
The Department of Chemistry Presents, via Online and In-person Presentation: Deepak Koirala, Assistant Professor, Department of Chemistry and Biochemistry UMBC
The genomes of many (+)-strand RNA viruses contain modular RNA domains that promote and regulate their translation and replication by exploiting the host cell machinery through noncanonical mechanisms. These domains serve as the platforms to recruit and assemble protein factors that form the functional ribonucleoprotein (RNP) complexes. Determination of the 3-dimensional structures of these RNAs and their interactions with the protein factors is a key to an in-depth understanding of these fundamental virological processes and developing antiviral drugs that target these structures. Yet, our knowledge of the 3-dimensional structures, interactions, and functional roles of these RNAs and RNP complexes remains largely unknown. Current research in my laboratory focuses on the structures and mechanisms of the enteroviral replication platform, picornavirus internal ribosome entry sites (IRESs), and tombusvirus 3ꞌ cap-independent translation enhancers (3ꞌCITEs) using a unique structural approach called Fab-assisted RNA crystallography. The most significant findings and ongoing research in my laboratory include 1) the determination of the first high-resolution crystal structures of the 5ꞌ cloverleaf-like RNA (5ꞌCL), a conserved domain essential for the enteroviral genome replication, that revealed the structural basis for 3C and PCBP protein binding and 2) the determination of the crystal structure of a cactus virus 3ꞌCITE, an RNA structure that mimics the mRNA 5ꞌ cap for eIF4E binding. In this seminar, I will discuss the knots and bolts of X-ray crystallography of these RNA structures and how they facilitate the recruitment of viral and cellular protein factors for viral genome replication and translation (unpublished results).
Professional Interests
RNA structures, functions and consequences
RNA structures associated with cap-independent viral translation
RNA structures associated with human repeat expansion disorders
Education & Training
Postdoc – The University of Chicago (2014 – 2020)
Ph.D. – Kent State University (2008 – 2014)
M.Sc. – Tribhuvan University, Nepal (2002 – 2004)
B.Sc. – Tribhuvan University, Nepal (1999 – 2002)