Aberrant RNA splicing produces alternative isoforms of genes to facilitate tumor progression,yet how this process is regulated by oncogenic signal remains largely unknown.Here,we unveil that non-canonical activation o...Aberrant RNA splicing produces alternative isoforms of genes to facilitate tumor progression,yet how this process is regulated by oncogenic signal remains largely unknown.Here,we unveil that non-canonical activation of nuclear AURKA promotes an oncogenic RNA splicing of tumor suppressor RBM4 directed by m^(6)A reader YTHDC1 in lung cancer.Nuclear translocation of AURKA is a prerequisite for RNA aberrant splicing,specifically triggering RBM4 splicing from the full isoform(RBM4-FL)to the short isoform(RBM4-S)in a kinase-independent manner.展开更多
基金We thank Quentin Liu’s lab members for their critical comments and technical support.We thank Eric W.-F.Lam for his critical reading of the manuscript and insightful suggestions.This research work was supported by the National Natural Science Foundation of China(No.81820108024 to Q.L.,No.81630005 to Q.L.,No.81830088 to Y.W.,No.81873441 to B.-L.J.,No.82103659 to S.-S.L.,No.8210113819 to Y.-F.Q.,No.81972786 to J.X.,No.82003141 to F.P.,No.82002960 to B.C.,No.31801100 to X.-.D.D.)National Key R&D Program of China(2019YFA0110300 to Q.L.and 2017YFA0505600-04 to Q.L.)+12 种基金Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China(No.IRT_17R15)Innovative Research Team in University of Liaoning(No.LT2017001 to Q.L.)Heilongjiang Postdoctoral Fund(No.LBH-Z20074 to S.-S.L.)Harbin Medical University Doctor Green Seedling Ground-breaking Project(No.QMPT-1909 to S.-S.L.)the Natural Science Foundation of Liaoning(No.2019-BS-081 to F.P.)the“Seedling cultivation”program for young scientific and technological talents of Liaoning(No.LZ2020044 to F.P.,No.LZ2019067 to B.C.)Dalian Science and Technology program-The central government guiding local funding projects for scientific and technological development(2021 to F.P.)Dalian High-level Talents Innovation Support Program-Young Science and Technology Star(2021RQ004 to B.C.)the program for climbing Scholars of Liaoning,the Science and Technology Innovation Foundation of Dalian(No.2020JJ25CY008 to Q.L.)International Scientific and Technological Cooperation of Dalian(2015F11GH095 to Q.L.)the Natural Science Foundation of Guangdong(2016A030311038 and 2017A030313608 to Q.L.)the Science and Technology Planning Project of Guangzhou(No.201804020044 to Q.L.)the Scientific Research Project of Guangzhou(No.201904010492 to B.-L.J.).
文摘Aberrant RNA splicing produces alternative isoforms of genes to facilitate tumor progression,yet how this process is regulated by oncogenic signal remains largely unknown.Here,we unveil that non-canonical activation of nuclear AURKA promotes an oncogenic RNA splicing of tumor suppressor RBM4 directed by m^(6)A reader YTHDC1 in lung cancer.Nuclear translocation of AURKA is a prerequisite for RNA aberrant splicing,specifically triggering RBM4 splicing from the full isoform(RBM4-FL)to the short isoform(RBM4-S)in a kinase-independent manner.
