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RAF1 mRNA translation initiation site (RAF1 mRNA) (RAF1 mRNA)

Target
RAF1 mRNA
Molecular classification
Nucleic acid, Messenger RNA (mRNA)
01

Overview

The RAF1 mRNA translation initiation site is the specific sequence within the RAF1 (c-Raf) messenger RNA where the translation machinery, including the ribosome and initiation factors, assembles to begin protein synthesis. RAF1 is a proto-oncogene encoding a serine/threonine kinase that acts as a pivotal mediator in the MAPK/ERK signaling pathway, which is responsible for transmitting extracellular signals to the nucleus to regulate cell growth, differentiation, and survival [UniProt, P04049]. Overexpression or constitutive activation of the RAF1 pathway is a common driver in various malignancies, including ovarian, renal, and lung cancers [PubMed, 8640144]. Therapeutic strategies targeting the mRNA translation initiation site, such as antisense oligonucleotides (ASOs), aim to silence the gene by preventing the production of the RAF1 protein altogether [PubMed, 10550078]. These ASOs bind to the target sequence via Watson-Crick base pairing, leading to either steric blockage of the ribosome or RNase H-mediated degradation of the mRNA transcript [PubMed, 9389983]. While the well-known antisense drug ISIS 5132 was designed to target the 3' untranslated region of RAF1 mRNA, the translation initiation site remains a significant target for RNA-based therapies designed to inhibit oncogenic signaling in solid tumors.

Other names
c-Raf mRNA translation initiation siteRAF1 translation start siteRAF1 mRNA AUG regionRAF1 translation initiation complex site
02

Mechanism of action

Antisense-mediated inhibition of translation through steric hindrance of the ribosome or RNase H-dependent mRNA degradation.

03

Biological functions

Protein synthesisSignal transductionCell proliferationCell survivalMAPK cascade regulation
04

Disease associations

CancerSolid tumorsOvarian cancerRenal cell carcinomaNon-small cell lung cancer
05

Safety considerations

Off-target RNA bindingImmune system activation (TLR signaling)ThrombocytopeniaComplement activationDelivery to target tissues
06

Interacting drugs

ISIS 5132

2 more in the full profile.

07

Biomarkers

RAF1 protein expression levelsPhospho-ERK1/2 levelsMAPK pathway activityRAF1 mRNA levels (RT-PCR)

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