Talk on Friday 03:42-03:54pm submitted by Niyati Jain
Phylogenetic, Structure and thermodynamic insight of HIV-1 Intronic splicing silencer (ISS)
Niyati Jain (Department of Chemistry, Case Western Reserve University), Brittany D. Rife (Department of Pathology, Immunology and Laboratory of Medicine, College of Medicine, and Emerging Pathogens Institute, University of Florida, Gainesville), Christopher E. Morgan (Department of Chemistry,Case Western Reserve University), Blanton S. Tolbert (Department of Chemistry,Case Western Reserve University)
Alternative splicing is a crucial process occurring during the human immunodeficiency virus type 1 (HIV-1) life cycle. This process is primarily regulated by interaction between the various splice sites within the viral RNA genome and trans host partners that regulate the splicing process by activating or repressing splice site usage. The host proteins hnRNP A1 and ASF regulate the splicing pattern in HIV-1 transcript by binding to highly conserved 3’splice site ssA7. Splice site A7 is 175 nucleotide long RNA and composed of 3 stem- loop structures that contain splicing regulatory elements ISS (SL1), ESE3 (SL2) and ESS3 (SL3) that bind to trans host proteins and thus regulate the splicing pattern .The mechanism by which this ssA7 recruits these host proteins and regulate the splicing pattern in HIV-1 is not well characterized. The high- resolution solution structure of ssA7 RNA and its interaction studies with its host factors will give the insight about the mechanism involved. Solving the NMR structure of large RNA like ssA7 is challenging and so we have applied divide and conquer approach. The ESS3 solution structure was recently solved and now we are focusing on Intron splicing silencer (ISS).
The ISS is a 50-nucleotide long stem-loop RNA with several non-canonical elements that may add to the dynamics and function of this molecule. Toward understanding the structure -based mechanism of the ISS function, NMR spectroscopy has been used to probe its solution properties. Here, we present a solution structure of ISS.
Keywords: HIV-1, Intronic splicing silencer, NMR