Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.4.4 (
kinesin
)
5,033
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
hCLE/C14orf166/RTRAF, DDX1, and HSPC117 are components of cytoplasmic mRNA-transporting granules
kinesin
-associated in dendrites. They have also been found in cytoplasmic ribosome-containing RNA granules that transport specific mRNAs halted for translation until specific neuronal signals renders them accessible to the translation machinery. hCLE associates to DDX1, HSPC117, and FAM98B in HEK293T cells and all four proteins bind to cap analog-containing resins. Competition and elution experiments indicate that binding of hCLE complex to cap resins is independent of
eIF4E
; the cap-binding factor needed for translation. Purified hCLE free of its associated proteins binds cap with low affinity suggesting that its interacting proteins modulate its cap association. hCLE silencing reduces hCLE accumulation and that of its interacting proteins and decreases mRNA translation. hCLE-associated RNAs have been isolated and sequenced; RNAs involved in mRNA translation are specifically associated. The data suggest that RNA granules may co-transport RNAs encoding proteins involved in specific functions together with RNAs that encode proteins needed for the translation of these specific RNAs and indicate an important role for hCLE modulating mRNA translation.
...
PMID:hCLE/RTRAF-HSPC117-DDX1-FAM98B: A New Cap-Binding Complex That Activates mRNA Translation. 3083 3
Viruses have transformed our understanding of mammalian RNA processing, including facilitating the discovery of the methyl-7-guanosine (m
7
G) cap on the 5' end of RNAs. The m
7
G cap is required for RNAs to bind the eukaryotic translation initiation factor
eIF4E
and associate with the translation machinery across plant and animal kingdoms. The potyvirus-derived viral genome-linked protein (VPg) is covalently bound to the 5' end of viral genomic RNA (gRNA) and associates with host
eIF4E
for successful infection. Divergent models to explain these observations proposed either an unknown mode of
eIF4E
engagement or a competition of VPg for the m
7
G cap-binding site. To dissect these possibilities, we resolved the structure of VPg, revealing a previously unknown 3-dimensional (3D) fold, and characterized the VPg-
eIF4E
complex using NMR and biophysical techniques. VPg directly bound the cap-binding site of
eIF4E
and competed for m
7
G cap analog binding. In human cells, VPg inhibited
eIF4E
-dependent RNA export, translation, and oncogenic transformation. Moreover, VPg formed trimeric complexes with
eIF4E
-eIF4G,
eIF4E
bound VPg-
luciferase
RNA conjugates, and these VPg-RNA conjugates were templates for translation. Informatic analyses revealed structural similarities between VPg and the human
kinesin
EG5. Consistently, EG5 directly bound
eIF4E
in a similar manner to VPg, demonstrating that this form of engagement is relevant beyond potyviruses. In all, we revealed an unprecedented modality for control and engagement of
eIF4E
and show that VPg-RNA conjugates functionally engage
eIF4E
. As such, potyvirus VPg provides a unique model system to interrogate
eIF4E
.
...
PMID:Structural studies of the eIF4E-VPg complex reveal a direct competition for capped RNA: Implications for translation. 3171 17
