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The RNA polymerase II subunit Rpb9 activates ATG1 transcription and autophagy.

ABSTRACT: Macroautophagy/autophagy is a conserved process in eukaryotic cells that mediates the degradation and recycling of intracellular substrates. Proteins encoded by autophagy-related (ATG) genes are essentially involved in the autophagy process and must be tightly regulated in response to various circumstances, such as nutrient-rich and starvation conditions. However, crucial transcriptional activators of ATG genes have remained obscure. Here, we identify the RNA polymerase II subunit Rpb9 as an essential regulator of autophagy by a high-throughput screen of a Saccharomyces cerevisiae gene knockout library. Rpb9 plays a crucial and specific role in upregulating ATG1 transcription, and its deficiency decreases autophagic activities. Rpb9 promotes ATG1 transcription by binding to its promoter region, which is mediated by Gcn4. Furthermore, the function of Rpb9 in autophagy and its regulation of ATG1/ULK1 transcription are conserved in mammalian cells. Together, our results indicate that Rpb9 specifically activates ATG1 transcription and thus positively regulates the autophagy process.

SUBMITTER: Huang T

PROVIDER: S-EPMC9638876 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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The RNA polymerase II subunit Rpb9 activates ATG1 transcription and autophagy.

Huang Ting T Jiang Gaoyue G Zhang Yabin Y Lei Yuqing Y Liu Shiyan S Li Huihui H Lu Kefeng K

EMBO reports 20220914 11

Macroautophagy/autophagy is a conserved process in eukaryotic cells that mediates the degradation and recycling of intracellular substrates. Proteins encoded by autophagy-related (ATG) genes are essentially involved in the autophagy process and must be tightly regulated in response to various circumstances, such as nutrient-rich and starvation conditions. However, crucial transcriptional activators of ATG genes have remained obscure. Here, we identify the RNA polymerase II subunit Rpb9 as an ess ...[more]

PMID: 36102592

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Project description:Rpb11 subunit of RNA polymerase II of Eukaryotes is related to N-terminal domain of eubacterial ? subunit and forms a complex with Rpb3 subunit analogous to prokaryotic ?2 homodimer, which is involved in RNA polymerase assembly and promoter recognition. In humans, a POLR2J gene family has been identified that potentially encodes several hRPB11 proteins differing mainly in their short C-terminal regions. The functions of the different human specific isoforms are still mainly unknown. To further characterize the minor human specific isoform of RNA polymerase II subunit hRPB11b?, the only one from hRPB11 (POLR2J) homologues that can replace its yeast counterpart in vivo, we used it as bait in a yeast two-hybrid screening of a human fetal brain cDNA library. By this analysis and subsequent co-purification assay in vitro, we identified transcription factor ATF4 as a prominent partner of the minor RNA polymerase II (RNAP II) subunit hRPB11b?. We demonstrated that the hRPB11b? interacts with leucine b-Zip domain located on the C-terminal part of ATF4. Overexpression of ATF4 activated the reporter more than 10-fold whereas co-transfection of hRPB11b? resulted in a 2.5-fold enhancement of ATF4 activation. Our data indicate that the mode of interaction of human RNAP II main (containing major for of hRPB11 subunit) and minor (containing hRPB11b? isoform of POLR2J subunit) transcription enzymes with ATF4 is certainly different in the two complexes involving hRPB3-ATF4 (not hRPB11a-ATF4) and hRpb11b?-ATF4 platforms in the first and the second case, respectively. The interaction of hRPB11b? and ATF4 appears to be necessary for the activation of RNA polymerase II containing the minor isoform of the hRPB11 subunit (POLR2J) on gene promoters regulated by this transcription factor. ATF4 activates transcription by directly contacting RNA polymerase II in the region of the heterodimer of ?-like subunits (Rpb3-Rpb11) without involving a Mediator, which provides fast and highly effective activation of transcription of the desired genes. In RNA polymerase II of Homo sapiens that contains plural isoforms of the subunit hRPB11 (POLR2J), the strength of the hRPB11-ATF4 interaction appeared to be isoform-specific, providing the first functional distinction between the previously discovered human forms of the Rpb11 subunit.

Dataset Information

The RNA polymerase II subunit Rpb9 activates ATG1 transcription and autophagy.

Publications

The RNA polymerase II subunit Rpb9 activates ATG1 transcription and autophagy.

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