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The Rapid tRNA Decay Pathway Monitors the Structural Integrity of Mature tRNAs
Author(s) -
Phizicky Eric M.,
Whipple Joseph M.,
Lane Elizabeth A.,
D'Silva Sonia
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.203.1
Subject(s) - transfer rna , structural integrity , computational biology , microbiology and biotechnology , chemistry , biology , genetics , rna , engineering , gene , structural engineering
tRNAs are highly modified and highly stable, and subject to several quality control steps during and after biosynthesis. Specific mature tRNA species lacking certain modifications are degraded in yeast by the Rapid tRNA Decay (RTD) pathway, mediated by the 5′‐3′ exonucleases Rat1 and Xrn1. However, it is unclear how substrate tRNAs are recognized, since only a subset of hypomodified species are degraded. We used a genetic system to identify determinants for the RTD pathway in cells lacking ac 4 C and Um, by examining variants of the substrate tRNA Ser(CGA) , or the non‐substrates tRNA Ser(IGA) and tRNA Ser(GCU) . Nearly all tRNA Ser(CGA) variants with predicted stabilizing substitutions in the acceptor or T‐stem restore mature tRNA levels, while anticodon stem substitutions have no effect. Conversely, non‐substrate tRNAs and fully modified tRNAs can be subject to RTD if appropriately destabilized. Analysis shows that RTD substrates have a less rigid structure than non‐substrates, have a more exposed 5′ end, and are more sensitive to Xrn1. These findings suggest that the RTD pathway monitors the structural integrity of the acceptor and T‐stems of mature tRNAs, imposing a lower threshold for their stability.