Talk abstracts
Talk on Friday 04:30-04:45pm submitted by Vishal Adhav
Structural basis for microRNA-length maintenance
Vishal Adhav (Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, 43210, USA.), Audrey Kehling (Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, 43210, USA.), Priyanshi Patel (Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, 43210, USA.), Kotaro Nakanishi (Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, 43210, USA.)
Abstract:
MicroRNAs (miRNAs) are critical small noncoding RNAs that guide Argonaute proteins to their target mRNAs for gene regulation. For this reason, miRNAs are typically about 22 nucleotides (nt) long. Although poly(A)-specific ribonuclease (PARN) trims the 3' ends of miRNA precursors and extended miRNAs to approximately 22 nt, the underlying molecular mechanism remains unclear. Here, using cryo-electron microscopy, we show that human PARN physically interacts with Argonaute, forming a composite molecular ruler that selectively recognizes longer miRNAs and trims their 3 ends through its 3'-5' exonuclease activity. Our structural snapshots visualize three distinct conformations corresponding to sampling, interrogation, and trimming states. In the sampling state, PARN's RRM and R3H domains act as a molecular clipper, capturing the 3' tail that loops out from Argonaute's nucleic acid-binding channel. This interrogation licenses the 3' ends of only long miRNAs for transfer from the Argonaute PAZ domain to PARN's nuclease active site. The composite molecular ruler limits exonucleolytic processing by PARN once the miRNA is shortened to ~22 nt. Together, these findings provide the first example of how two proteins work together to measure and adjust RNA length. In addition, our structure provides a long-sought explanation for how PARN preferentially trims the poly(A) tails of mRNAs.
Keywords: Argonaute, PARN, miRNAs