Decoding the 5′ nucleotide bias of PIWI-interacting RNAs

Chad B. Stein, Pavol Genzor, Sanga Mitra, Alexandra R. Elchert, Jonathan J. Ipsaro, Leif Benner, Sushil Sobti, Yijun Su, Molly Hammell, Leemor Joshua-Tor and Astrid D. Haase ()
Additional contact information
Chad B. Stein: National Institutes of Health
Pavol Genzor: National Institutes of Health
Sanga Mitra: National Institutes of Health
Alexandra R. Elchert: National Institutes of Health
Jonathan J. Ipsaro: Howard Hughes Medical Institute
Leif Benner: National Institutes of Health
Sushil Sobti: National Institutes of Health
Yijun Su: National Institutes of Health
Molly Hammell: Cold Spring Harbor Laboratory
Leemor Joshua-Tor: Howard Hughes Medical Institute
Astrid D. Haase: National Institutes of Health

Nature Communications, 2019, vol. 10, issue 1, 1-8

Abstract: Abstract PIWI-interacting RNAs (piRNAs) are at the center of a small RNA-based immune system that defends genomes against the deleterious action of mobile genetic elements (transposons). PiRNAs are highly variable in sequence with extensive targeting potential. Their diversity is restricted by their preference to start with a Uridine (U) at the 5′ most position (1U-bias), a bias that remains poorly understood. Here we uncover that the 1U-bias of Piwi-piRNAs is established by consecutive discrimination against all nucleotides but U, first during piRNA biogenesis and then upon interaction with Piwi’s specificity loop. Sequence preferences during piRNA processing also restrict U across the piRNA body with the potential to directly impact target recognition. Overall, the uncovered signatures could modulate specificity and efficacy of piRNA-mediated transposon restriction, and provide a substrate for purifying selection in the ongoing arms race between genomes and their mobile parasites.

Date: 2019
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DOI: 10.1038/s41467-019-08803-z

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