TY - JOUR
T1 - A potential role for initiator-tRNA in pre-mRNA splicing regulation
AU - Kamhi, Eyal
AU - Raitskin, Oleg
AU - Sperling, Ruth
AU - Sperling, Joseph
PY - 2010/6/22
Y1 - 2010/6/22
N2 - The translation initiator-tRNA plays a crucial role in the initiation of protein synthesis in both prokaryotic and eukaryotic cells, by employing specific base pairing between its anticodon triplet CAU and the general initiation codon AUG in the mRNA. Here we show that the initiator-tRNA may also act, in a manner that is independent of its role in protein translation, as a pre-mRNA splicing regulator. Specifically, we show that alternative splicing events that are induced by mutations in the translation initiation AUG codon can be suppressed by expressing initiator-tRNA constructs carrying anticodon mutations that compensate for the AUG mutations. These mutated initiator-tRNAs appeared to be uncharged with an amino acid. Our results imply that recognition of the initiation AUG sequence by the anticodon triplet of initiator-tRNA in its unloaded state plays a role in quality control of splicing in the cell nucleus by a yet unresolved mechanism. Identifying the initiatort-RNA as a transacting splicing regulator suggests a novel involvement of this molecule in splicing regulation and provides a critical step toward deciphering this intriguing mechanism.
AB - The translation initiator-tRNA plays a crucial role in the initiation of protein synthesis in both prokaryotic and eukaryotic cells, by employing specific base pairing between its anticodon triplet CAU and the general initiation codon AUG in the mRNA. Here we show that the initiator-tRNA may also act, in a manner that is independent of its role in protein translation, as a pre-mRNA splicing regulator. Specifically, we show that alternative splicing events that are induced by mutations in the translation initiation AUG codon can be suppressed by expressing initiator-tRNA constructs carrying anticodon mutations that compensate for the AUG mutations. These mutated initiator-tRNAs appeared to be uncharged with an amino acid. Our results imply that recognition of the initiation AUG sequence by the anticodon triplet of initiator-tRNA in its unloaded state plays a role in quality control of splicing in the cell nucleus by a yet unresolved mechanism. Identifying the initiatort-RNA as a transacting splicing regulator suggests a novel involvement of this molecule in splicing regulation and provides a critical step toward deciphering this intriguing mechanism.
KW - 5′ splice site
KW - Alternative splicing
KW - Premature termination codon
KW - Spliceosome
KW - Suppression of splicing
UR - http://www.scopus.com/inward/record.url?scp=77954948738&partnerID=8YFLogxK
U2 - 10.1073/pnas.0911561107
DO - 10.1073/pnas.0911561107
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C2 - 20534564
AN - SCOPUS:77954948738
SN - 0027-8424
VL - 107
SP - 11319
EP - 11324
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 25
ER -