Projects per year
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 synthesised 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 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 stabilises RNMT and thus is critical for cellular cap methylation and cell viability. Here 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 stabilise RNMT. RAM functions in the nucleus and we report that nuclear import of RAM is dependent on PY nuclear localisation signals and Kapß2 nuclear transport protein.
Original language | English |
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Pages (from-to) | 473-484 |
Number of pages | 12 |
Journal | Biochemical Journal |
Volume | 457 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1 Feb 2014 |
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Dive into the research topics of 'RAM function is dependent on Kapβ2-mediated nuclear entry'. Together they form a unique fingerprint.Projects
- 2 Finished
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Investigating MRNA Methyl Cap Regulation, Function and Therapeutic Potential (Senior Non-Clinical Fellowship)
Cowling, V. (Investigator)
1/01/14 → 31/12/21
Project: Research
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Aref#d: 19352. The Mechanism of Myc function in cell proliferation and cancer (Career Development Fellowship)
Cowling, V. (Investigator)
3/12/07 → 2/01/14
Project: Research