Elevated P-TEFb activity triggers negative feedback in translation to limit intestinal tumorigenesis

ABSTRACT: Enhanced P-TEFb activity is thought to promote cell proliferation by increasing the transcriptional output of RNA polymerase II, and normally most cellular P-TEFb is inhibited by 7SK snRNP containing LARP7 and HEXIM1. Recent genomic studies have linked inactivation of LARP7 to distinct human diseases at opposite ends of the proliferation spectrum, both insufficient growth disorder and uncontrolled proliferation in cancer, although neither has been experimentally validated in animal models. Here, we report that conditional knockout of Larp7 suppresses intestinal tumorigenesis in ApcMin/+ mice. We find that loss of Larp7 elevates P-TEFb activity to decrease the expression of ribosomal biogenesis factor Bms1, leading to Trp53 activation and attenuated translation of DNA replication factor

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Homo sapiens

SUBMITTER: chao yang 

PROVIDER: E-MTAB-17585 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress