RAM Function is Dependent on Kapβ2-mediated Nuclear Entry

Overview

Journal Biochem J

Specialty Biochemistry

Date 2013 Nov 9

PMID 24200467

Citations 14

Authors

Thomas Gonatopoulos-Pournatzis

Victoria H Cowling

Affiliations

Soon will be listed here.

Abstract

Eukaryotic gene expression is dependent on the modification of the first transcribed nucleotide of pre-mRNA by the addition of the 7-methylguanosine cap. The cap protects transcripts from exonucleases and recruits complexes which mediate transcription elongation, processing and translation initiation. The cap is synthesized by a series of reactions which link 7-methylguanosine to the first transcribed nucleotide via a 5' to 5' triphosphate bridge. In mammals, cap synthesis is catalysed by the sequential action of RNGTT (RNA guanylyltransferase and 5'-phosphatase) and RNMT (RNA guanine-7 methyltransferase), enzymes recruited to RNA pol II (polymerase II) during the early stages of transcription. We recently discovered that the mammalian cap methyltransferase is a heterodimer consisting of RNMT and the RNMT-activating subunit RAM (RNMT-activating mini-protein). RAM activates and stabilizes RNMT and thus is critical for cellular cap methylation and cell viability. In the present study we report that RNMT interacts with the N-terminal 45 amino acids of RAM, a domain necessary and sufficient for maximal RNMT activation. In contrast, smaller components of this RAM domain are sufficient to stabilize RNMT. RAM functions in the nucleus and we report that nuclear import of RAM is dependent on PY nuclear localization signals and Kapβ2 (karyopherin β2) nuclear transport protein.

Citing Articles

RAM is upregulated during T cell activation and is required for RNA cap formation and gene expression.

Knop K, Gomez-Moreira C, Galloway A, Ditsova D, Cowling V Discov Immunol. 2024; 3(1):kyad021.

PMID: 38572449 PMC: 10989996. DOI: 10.1093/discim/kyad021.

A new Karyopherin-β2 binding PY-NLS epitope of HNRNPH2 linked to neurodevelopmental disorders.

Gonzalez A, Kim H, Freibaum B, Fung H, Brautigam C, Taylor J Structure. 2023; 31(8):924-934.e4.

PMID: 37279758 PMC: 10524338. DOI: 10.1016/j.str.2023.05.010.

The RNA cap methyltransferases RNMT and CMTR1 co-ordinate gene expression during neural differentiation.

Liang S, Almohammed R, Cowling V Biochem Soc Trans. 2023; 51(3):1131-1141.

PMID: 37145036 PMC: 10317164. DOI: 10.1042/BST20221154.

Upregulation of RNA cap methyltransferase RNMT drives ribosome biogenesis during T cell activation.

Galloway A, Kaskar A, Ditsova D, Atrih A, Yoshikawa H, Gomez-Moreira C Nucleic Acids Res. 2021; 49(12):6722-6738.

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From canonical to modified nucleotides: balancing translation and metabolism.

Accornero F, Ross R, Alfonzo J Crit Rev Biochem Mol Biol. 2020; 55(6):525-540.

PMID: 32933330 PMC: 7703805. DOI: 10.1080/10409238.2020.1818685.

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