The translational control of oncoprotein expression is implicated in many cancers. Here we report an eIF4A RNA helicase-dependent mechanism of translational control that contributes to oncogenesis and underlies the anticancer effects of silvestrol and related compounds. For example, eIF4A promotes T-cell acute lymphoblastic leukaemia development in vivo and is required for leukaemia maintenance. Accordingly, inhibition of eIF4A with silvestrol has powerful therapeutic effects against murine and human leukaemic cells in vitro and in vivo. We use transcriptome-scale ribosome footprinting to identify the hallmarks of eIF4A-dependent transcripts. These include 5' untranslated region (UTR) sequences such as the 12-nucleotide guanine quartet (CGG)4 motif that can form RNA G-quadruplex structures. Notably, among the most eIF4A-dependent and silvestrol-sensitive transcripts are a number of oncogenes, superenhancer-associated transcription factors, and epigenetic regulators. Hence, the 5' UTRs of select cancer genes harbour a targetable requirement for the eIF4A RNA helicase.
Pharmacology, Toxicology and Pharmaceutical Science
15
2%
Other
34
5%
Unknown
136
20%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 39. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 September 2026.
All research outputs
#1,238,271
of 31,634,113 outputs
Outputs from Nature
#37,019
of 111,765 outputs
Outputs of similar age
#10,259
of 258,295 outputs
Outputs of similar age from Nature
#496
of 971 outputs
Altmetric has tracked 31,634,113 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 111,765 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 98.0. This one has gotten more attention than average, scoring higher than 66% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 258,295 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 96% of its contemporaries.
We're also able to compare this research output to 971 others from the same source and published within six weeks on either side of this one. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.
