Ask about this productRelated genes to: THUMPD2 antibody
- Gene:
- THUMPD2 NIH gene
- Name:
- THUMP domain containing 2
- Previous symbol:
- C2orf8
- Synonyms:
- MGC2454
- Chromosome:
- 2p22.1
- Locus Type:
- gene with protein product
- Date approved:
- 2003-07-04
- Date modifiied:
- 2016-10-05
Related products to: THUMPD2 antibody
Related articles to: THUMPD2 antibody
- The internal stem loop (ISL) of the human U6 snRNA, which catalyzes pre-mRNA splicing, contains LARP7-dependent, snoRNA-guided 2'-O-methylations and an N-methylguanosine (mG) that is required for splicing of weak splice sites. Here, we show that installation of mG by the THUMPD2-TRMT112 methyltransferase complex is one of the last maturation events during U6 snRNP biogenesis. We dissect features of THUMPD2 required for association with U6 and present an experimentally validated model of the THUMPD2-TRMT112-U6 complex. Using in vitro methylation assays as well as a newly developed mG-sensitive deoxyribozyme to monitor U6-mG levels in cellular RNAs, we reveal that 2'-O-methylations within the U6 ISL enhance methylation of G. We show that mG and the 2'-O-methylations in U6 independently and interdependently influence alternative splicing. Furthermore, our data demonstrate that 2'-O-methylations in the ISL are required for incorporation of U6 into snRNPs whereas mG influences the progression of the U6 snRNP into larger assemblies, highlighting distinct roles of these modifications during spliceosome assembly. - Source: PubMed
Publication date: 2026/04/24
Kleiber NicolePetrosyan JonnyGreve MariaThomé Chairini CDybkov OlexandrTay Laurianne L EWelp Luisa MHackert PhilippTouboul DavidStark HolgerBohnsack Markus TUrlaub HenningHerzel LydiaGraille MarcHöbartner ClaudiaBohnsack Katherine E - Ovarian cancer (OC) is a common and lethal gynaecological malignancy. RNA-binding proteins (RBPs) play a crucial role in governing RNA metabolism and have been implicated in the development and progression of diverse cancer types. Slight alterations in RBPs' expression or activity can induce substantial modifications in the regulatory network. THUMPD2, as member of the RBP family, was found to have differential expression in ovarian cancer, with the mechanism has not been studied yet. In this study, THUMPD2 protein was found to be weakly expressed in the early (I + II) stages of OC (P = 0.013), with a low expression rate of 78.6 %, and highly expressed in late (III + IV) stages (P = 0.009), with a high expression rate of 84.8 %. The shRNA-mediated knockdown of THUMPD2 in OVCAR3 and SKOV3 cells resulted in increased cell proliferation but inhibited metastasis, whereas THUMPD2 overexpression had the opposite effect. THUMPD2 overexpression suppressed tumour growth in vivo. Conversely, low THUMPD2 expression promoted tumour growth. Furthermore, we identified the potential target genes and pathways of THUMPD2 using GO and KEGG analyses, which were related to the centrosome, microtubules, cell cycle, and extracellular matrix. We demonstrated that low expression of THUMPD2 in the early stage promoted tumour growth and high expression in the late stage promoted tumour metastasis. Our findings reveal the dual function of THUMPD2 in OC and suggest that THUMPD2 may serve as a therapeutic target for the treatment of OC. - Source: PubMed
Publication date: 2024/06/25
Hua MinhuiChen YujieJia MeiqunLv WenxuanXu YunzhaoZhang Yuquan - The mechanisms by which the relatively conserved spliceosome manages the enormously large number of splicing events that occur in humans (∼200 000 versus ∼300 in yeast) are poorly understood. Here, we show deposition of one RNA modification-N2-methylguanosine (m2G) on the G72 of U6 snRNA (the catalytic center of the spliceosome) promotes efficient pre-mRNA splicing activity in human cells. This modification was identified to be conserved among vertebrates. Further, THUMPD2 was demonstrated as the methyltransferase responsible for U6 m2G72 by explicitly recognizing the U6-specific sequences and structural elements. The knock-out of THUMPD2 eliminated U6 m2G72 and impaired the pre-mRNA splicing activity, resulting in thousands of changed alternative splicing events of endogenous pre-mRNAs in human cells. Notably, the aberrantly spliced pre-mRNA population elicited the nonsense-mediated mRNA decay pathway. We further show that THUMPD2 was associated with age-related macular degeneration and retinal function. Our study thus demonstrates how an RNA epigenetic modification of the major spliceosome regulates global pre-mRNA splicing and impacts physiology and disease. - Source: PubMed
Yang Wen-QingGe Jian-YangZhang XiaofengZhu Wen-YuLin LinShi YigongXu BeisiLiu Ru-Juan - Modified nucleotides in non-coding RNAs, such as tRNAs and snRNAs, represent an important layer of gene expression regulation through their ability to fine-tune mRNA maturation and translation. Dysregulation of such modifications and the enzymes installing them have been linked to various human pathologies including neurodevelopmental disorders and cancers. Several methyltransferases (MTases) are regulated allosterically by human TRMT112 (Trm112 in Saccharomyces cerevisiae), but the interactome of this regulator and targets of its interacting MTases remain incompletely characterized. Here, we have investigated the interaction network of human TRMT112 in intact cells and identify three poorly characterized putative MTases (TRMT11, THUMPD3 and THUMPD2) as direct partners. We demonstrate that these three proteins are active N2-methylguanosine (m2G) MTases and that TRMT11 and THUMPD3 methylate positions 10 and 6 of tRNAs, respectively. For THUMPD2, we discovered that it directly associates with the U6 snRNA, a core component of the catalytic spliceosome, and is required for the formation of m2G, the last 'orphan' modification in U6 snRNA. Furthermore, our data reveal the combined importance of TRMT11 and THUMPD3 for optimal protein synthesis and cell proliferation as well as a role for THUMPD2 in fine-tuning pre-mRNA splicing. - Source: PubMed
Wang CanUlryck NathalieHerzel LydiaPythoud NicolasKleiber NicoleGuérineau VincentJactel VincentMoritz ChloéBohnsack Markus TCarapito ChristineTouboul DavidBohnsack Katherine EGraille Marc - Tick-borne encephalitis virus (TBEV), the most medically relevant tick-transmitted flavivirus in Eurasia, targets the host central nervous system and frequently causes severe encephalitis. The severity of TBEV-induced neuropathogenesis is highly cell-type specific and the exact mechanism responsible for such differences has not been fully described yet. Thus, we performed a comprehensive analysis of alterations in host poly-(A)/miRNA/lncRNA expression upon TBEV infection in human primary neurons (high cytopathic effect) and astrocytes (low cytopathic effect). Infection with severe but not mild TBEV strain resulted in a high neuronal death rate. In comparison, infection with either of TBEV strains in human astrocytes did not. Differential expression and splicing analyses with an prediction of miRNA/mRNA/lncRNA/vd-sRNA networks found significant changes in inflammatory and immune response pathways, nervous system development and regulation of mitosis in TBEV Hypr-infected neurons. Candidate mechanisms responsible for the aforementioned phenomena include specific regulation of host mRNA levels via differentially expressed miRNAs/lncRNAs or vd-sRNAs mimicking endogenous miRNAs and virus-driven modulation of host pre-mRNA splicing. We suggest that these factors are responsible for the observed differences in the virulence manifestation of both TBEV strains in different cell lines. This work brings the first complex overview of alterations in the transcriptome of human astrocytes and neurons during the infection by two TBEV strains of different virulence. The resulting data could serve as a starting point for further studies dealing with the mechanism of TBEV-host interactions and the related processes of TBEV pathogenesis. - Source: PubMed
Publication date: 2022/05/30
Selinger MartinVěchtová PavlínaTykalová HanaOšlejšková PetraRumlová MichaelaŠtěrba JánGrubhoffer Libor