Alu-Sc-mediated exonization generated a mitochondrial LKB1 gene variant found only in higher order primates

Abstract The tumor suppressor LKB1/STK11 plays important roles in regulating cellular metabolism and stress responses and its mutations are associated with various cancers. We recently identified a novel exon 1b within intron 1 of human LKB1/STK11, which generates an alternatively spliced, mitochond...

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Main Authors: Ivan Tan, Sonia Chothani, Hong-Hwa Lim, Kong-Peng Lam
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-86789-z
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author Ivan Tan
Sonia Chothani
Hong-Hwa Lim
Kong-Peng Lam
author_facet Ivan Tan
Sonia Chothani
Hong-Hwa Lim
Kong-Peng Lam
author_sort Ivan Tan
collection DOAJ
description Abstract The tumor suppressor LKB1/STK11 plays important roles in regulating cellular metabolism and stress responses and its mutations are associated with various cancers. We recently identified a novel exon 1b within intron 1 of human LKB1/STK11, which generates an alternatively spliced, mitochondria-targeting LKB1 isoform important for regulating mitochondrial oxidative stress. Here we examined the formation of this novel exon 1b and uncovered its relatively late emergence during evolution. Analyses of putative exon 1b genomic sequences within the primate superfamily indicated that the exonization of LKB1/STK11 exon 1b was mediated by the conserved retrotransposable element Alu-Sc. While putative exon 1b sequences are recognizable in most members of the primate family from New World Monkeys onwards, characteristically functional LKB1/STK11 exon 1b, with translation start and 5ʹ and 3ʹ splice sites, could only be found in greater apes and human, and interestingly, correlates with their increased body mass and longevity development.
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institution Kabale University
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spelling doaj-art-2bafb58410354f11b9d95a80bdb09f262025-02-02T12:17:01ZengNature PortfolioScientific Reports2045-23222025-01-011511610.1038/s41598-025-86789-zAlu-Sc-mediated exonization generated a mitochondrial LKB1 gene variant found only in higher order primatesIvan Tan0Sonia Chothani1Hong-Hwa Lim2Kong-Peng Lam3Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR)Duke-NUS Medical SchoolSingapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR)Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR)Abstract The tumor suppressor LKB1/STK11 plays important roles in regulating cellular metabolism and stress responses and its mutations are associated with various cancers. We recently identified a novel exon 1b within intron 1 of human LKB1/STK11, which generates an alternatively spliced, mitochondria-targeting LKB1 isoform important for regulating mitochondrial oxidative stress. Here we examined the formation of this novel exon 1b and uncovered its relatively late emergence during evolution. Analyses of putative exon 1b genomic sequences within the primate superfamily indicated that the exonization of LKB1/STK11 exon 1b was mediated by the conserved retrotransposable element Alu-Sc. While putative exon 1b sequences are recognizable in most members of the primate family from New World Monkeys onwards, characteristically functional LKB1/STK11 exon 1b, with translation start and 5ʹ and 3ʹ splice sites, could only be found in greater apes and human, and interestingly, correlates with their increased body mass and longevity development.https://doi.org/10.1038/s41598-025-86789-zIntronExonSINEAlu elementsPrimatesEvolution
spellingShingle Ivan Tan
Sonia Chothani
Hong-Hwa Lim
Kong-Peng Lam
Alu-Sc-mediated exonization generated a mitochondrial LKB1 gene variant found only in higher order primates
Scientific Reports
Intron
Exon
SINE
Alu elements
Primates
Evolution
title Alu-Sc-mediated exonization generated a mitochondrial LKB1 gene variant found only in higher order primates
title_full Alu-Sc-mediated exonization generated a mitochondrial LKB1 gene variant found only in higher order primates
title_fullStr Alu-Sc-mediated exonization generated a mitochondrial LKB1 gene variant found only in higher order primates
title_full_unstemmed Alu-Sc-mediated exonization generated a mitochondrial LKB1 gene variant found only in higher order primates
title_short Alu-Sc-mediated exonization generated a mitochondrial LKB1 gene variant found only in higher order primates
title_sort alu sc mediated exonization generated a mitochondrial lkb1 gene variant found only in higher order primates
topic Intron
Exon
SINE
Alu elements
Primates
Evolution
url https://doi.org/10.1038/s41598-025-86789-z
work_keys_str_mv AT ivantan aluscmediatedexonizationgeneratedamitochondriallkb1genevariantfoundonlyinhigherorderprimates
AT soniachothani aluscmediatedexonizationgeneratedamitochondriallkb1genevariantfoundonlyinhigherorderprimates
AT honghwalim aluscmediatedexonizationgeneratedamitochondriallkb1genevariantfoundonlyinhigherorderprimates
AT kongpenglam aluscmediatedexonizationgeneratedamitochondriallkb1genevariantfoundonlyinhigherorderprimates