IndraLab

Statements

METTL3 binds EIF3H. 40 / 40
| 10 30
reach
"The interaction between METTL3 and eIF3h is essential for translation and oncogenic transformation in lung cancer (31)."
34568001
sparser
"Mechanistically, exosomal circLPAR1 was internalized by CRC cells, and it suppressed tumor growth, likely because exosomal circLPAR1 directly bound with eIF3h specifically suppressed the METTL3-eIF3h interaction, decreasing the translation of oncogene BRD4."
35164758
sparser
"We next tested the functional interaction between METTL3 and eIF3h, and found depletion of eIF3h abrogated the enhanced translation by METTL3 ( xref and xref )."
30232453
sparser
"In particular mRNA looping generated by METTL3-eIF3h interaction enhances translation of a large subset of oncogenic mRNAs, paving the way for the development of new cancer therapeutic strategies [ xref ]."
33202605
sparser
"In mammals, a direct functional and physical interaction between METTL3 and eIF3h supports the mRNA looping mechanism for ribosome recycling and translational control [ xref ], since eIF3 is essential for the attachment of the recycled 40S subunits to mRNA to start a new round [ xref , xref ]."
34070794
sparser
"In addition, direct physical and functional interactions between eIF3h and METTL3 have been reported to be required for enhanced translation of oncogenic mRNAs, formation of densely packed polyribosomes and oncogenic transformation of lung adenocarcinoma ( xref )."
36118041
sparser
"The METTL3-eIF3h interaction is required for enhanced translation, formation of densely packed polyribosomes, and oncogenic transformation."
30232453
sparser
"This is supported by; 1) the position-dependent effects of METTL3 tethering on mRNA translation, 2) EM visualization of METTL3 bound to endogenous polyribosomes and its proximity to cap-binding proteins, 3) METTL3 interaction with eIF3h, and 4) Disruption of METTL3-eIF3h interaction abolishes the ability of METTL3 to promote translation, affect polysome conformation, or promote oncogenic transformation."
30232453
sparser
"For example, METTL3, METTL14 and WTAP compose a complex that promotes the localization of MTC at nuclear speckles [ xref ] and METTL3 interacts with eIF3h to enhance mRNA translation [ xref ]."
33808751
reach
"We next tested the functional interaction between METTL3 and eIF3h, and found depletion of eIF3h abrogated the enhanced translation by METTL3 (XREF_FIG and XREF_FIG)."
30232453
sparser
"Finally, upon knockdown of METTL3, endogenous BRD4 expression is strongly reduced, independently of mRNA abundance, leading to the discovery that METTL3-eIF3h mediates N 6 -methyladenosine (m 6 A) modification ( xref ) and circularization of BRD4 mRNA to enhance translation and promote oncogenesis ( xref ) ( xref )."
34540900
sparser
"This occurs through direct binding of METTL3 to eIF3h."
32279082
sparser
"Considering that 1-200 aa is sufficient to directly interact with eIF3h ( xref and xref ) and that 1-200 aa can promote translation in tethering experiments whereas 1-150 aa does not ( xref ), we reasoned that a region between 150-200 aa must be important for the physical and functional METTL3-eIF3h interaction."
30232453
reach
"This is supported by; 1) the position dependent effects of METTL3 tethering on mRNA translation, 2) EM visualization of METTL3 bound to endogenous polyribosomes and its proximity to cap binding proteins, 3) METTL3 interaction with eIF3h, and 4) Disruption of METTL3-eIF3h interaction abolishes the ability of METTL3 to promote translation, affect polysome conformation, or promote oncogenic transformation."
30232453
sparser
"In addition, Choe et al ( xref ) identified a direct interaction between METTL3 and eukaryotic translation initiation factor 3 subunit H and revealed that this interaction served a crucial role in translation, densely packed polyribosome formation and oncogenic transformation."
33082869
sparser
"Choe et al. showed that the METTL3-eIF3h complex enhances the translation of bromodomain containing 4 (BRD4), which is also modified by m 6 A in lung cancer cells when tethered to reporter mRNA at sites near the stop codon, supporting an mRNA looping mechanism for ribosome recycling and translational control ( xref , xref )."
31921660
sparser
"It was reported that exosomal circLPAR1 could serve as a sponge of eIF3h to inhibit the METTL3–eIF3h interaction and affect BRD4 protein expression, thereby suppressing colorectal cancer development [ xref ]."
36139074
reach
"Interestingly, the oncogenic function of METTL3 in NSCLC is complicated, where METTL3 could methylate YAP mRNA and recruit YTHDF1/3 and eIF3b to promote translation of YAP mRNA, or could interact with eIF3h to promote translation of target mRNAs (e.g., BRD4) independent of its enzymatic activity."
32183948
sparser
"In the cytoplasm of lung cancer cells, METTL3 enhances translation efficiency of mRNA by recognizing the m6A in 3′UTR based on the interaction between METTL3 and eIF3h which are co-overexpressed in many types of cancer [ xref ]."
34103054
sparser
"It has been found that stem cells can be differentiated into malignant cells under unfavorable microenvironments. xref Although most of the current support for malignant tumors stems from the malignant transformation of stem cells, the mechanism of stem cell deterioration is still controversial. xref , xref For example, METTL3-eIF3h promotes stem cell deterioration, xref and farnesoid X receptor (FXR) regulates the proliferation of small-intestinal cancer stem cells (CSCs). xref , xref , xref C-Myc is related to the malignant differentiation of leukemia stem cells. xref Studies have found that JAK/STAT is highly activated in tumor stem cells. xref Studies have confirmed that liver CSCs are closely related to the recurrence of liver cancer. xref It is not clear what causes the accumulation of genetic errors of stem cells and changes in telomere function, which eventually evolve into malignant stem cells."
33425489
sparser
"Thus, future efforts aimed at inhibiting the METTL3-eIF3h association may lead to the development of new cancer therapies."
| PMC
sparser
"Previous studies showed that besides the YTHDF1-eIF3 looping model, m 6 A modifications localized to 5′UTRs can recruit eIF3 directly to induce translation, independent of eIF4E cap binding xref ; the m 6 A sites close to the stop codon can also form an mRNA loop through the interaction between METTL3 and eIF3h, enhancing mRNA translation xref ."
36195598
sparser
"The interaction between eIF3h with METTL3 was further confirmed using a α-METTL3 antibody (that recognizes a 1-250 aa METTL3 epitope) to specifically disrupt this eIF3h-METTL3 interaction ( xref )."
30232453
reach
"For example, METTL3, METTL14 and WTAP compose a complex that promotes the localization of MTC at nuclear speckles [XREF_BIBR] and METTL3 interacts with eIF3h to enhance mRNA translation [XREF_BIBR]."
33808751
sparser
"We find that METTL3 promotes translation of a large subset of oncogenic mRNAs and that METTL3-eIF3h interaction is required for oncogenic transformation."
30232453
reach
"METTL3 directly binds to the eukaryotic translation initiation factor 3 subunit h (eIF3h) and presumably promotes translation through ribosome recycling [63]."
34560891
sparser
"We next examined the relevance of the METTL3-eIF3h interaction and mRNA looping in the context of cancer cell biology."
30232453
reach
"METTL3 can interact with the transcription factor eIF3h to promote the translation of oncogenes and ultimately to catalyze and accelerate tumor growth and metastasis."
33643384
sparser
"Three subunits of the eukaryotic initiation factor 3 (eIF3) complex are correlated with cancer development—subunit eIF3d possesses cap-binding activity [ xref ]; eIF3G is associated with cancer progression; eIF3h interacts with METTL3 [ xref , xref ]."
33808751
sparser
"Further studies showed that this translation promotion effect depends on interaction between METTL3 and eIF3h, which are coordinately overexpressed in many types of cancers ( xref )."
31100245
reach
"METTL3 interacts with eIF3h to enhance the translation efficiency of target mRNAs including BRD4."
30266810
sparser
"Unexpectedly, cytoplasmic METTL3 could interact with eIF3h to enhance translation, suggesting that METTL3 might directly regulate translation in a m 6 A reader-independent manner ( xref ; xref )."
32850871
sparser
"METTL3 can interact with the transcription factor eIF3h to promote the translation of oncogenes and ultimately to catalyze and accelerate tumor growth and metastasis (Lin et al., xref ; Choe et al., xref )."
33643384
sparser
"Overall, our results support a model whereby mRNA circularization and translation control is mediated by a specific METTL3-eIF3h interaction ( xref )."
30232453
reach
"In the cytoplasm of lung cancer cells, METTL3 enhances translation efficiency of mRNA by recognizing the m6A in 3′UTR based on the interaction between METTL3 and eIF3h which are co-overexpressed in many types of cancer [24]."
34103054
sparser
"On the other hand, new evidence of functional mRNA cyclization came from recent studies of m 6 A mRNA methylation that brings 5′ and 3′ UTRs together via eIF3h–METTL3 interaction and/or cap/eIF4F/eIF3/YTHDF1/m6A bridge formation, which facilitates translation during oncogenesis [ xref , xref ]."
32121426
sparser
"Exosomal circLPAR1 functions in colorectal cancer diagnosis and tumorigenesis through suppressing BRD4 via METTL3-eIF3h interaction."
35164758
reach
"Choe et al. showed that the METTL3-eIF3h complex enhances the translation of bromodomain containing 4 (BRD4), which is also modified by m A in lung cancer cells when tethered to reporter mRNA at sites near the stop codon, supporting an mRNA looping mechanism for ribosome recycling and translational control (33, 69)."
31921660
sparser
"Novel loci implicated in BIR included olfactory receptors, the G0S2 oncogene/tumor suppressor axis, the EIF3H-METTL3 translational regulator, and the SUDS3 subunit of the Sin3A corepressor."
36833325
sparser
"Notably, in contrast to wild-type METTL3, forced expression of either a catalytically inactive mutant or METTL3 (A155), which disrupts the interaction of METTL3 with translation initiation factors eIF3h, is unable to promote the invasive capability of lung fibroblasts [ xref ]."
| PMC