Ribosome 18S m6A Methyltransferase METTL5 Promotes Translation Initiation and Breast Cancer Cell Growth

Rong, Bowen; Zhang, Qian; Wan, Jinkai; Xing, Shenghui; Dai, Ruofei; Li, Yuan; Cai, Jia‐Bin; Xie, Jiaying; Song, Yang; Chen, Jiawei; Zhang, Lei; Yan, Guoquan; Zhang, Wen; Gao, Hai; Han, Jing‐Dong J.; Qu, Qianhui; Ma, Honghui; Tian, Ye; Lan, Fei

doi:10.1016/j.celrep.2020.108544

Cited by 81 publications

(94 citation statements)

References 52 publications

(118 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They were correlated with METTL5 (writer), RBM15 (writer), IGF2BP1 (reader), and YTHDC1 (reader), respectively. Among the four m6A regulators, METTL5 was confirmed to serve as the enzyme for the m6A modification of 18S rRNA, thereby promoting breast cancer cell growth [45]. RBM15 was identified as a regulator that binds to METTL3 and WTAP and directs these two proteins to specific RNA sites for m6A modification [2].…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of lncRNAs involved in m6A regulation for patients with ovarian cancer

et al. 2021

View full text Add to dashboard Cite

Background Both N6-methyladenosine (m6A) modification and lncRNAs play an important role in the carcinogenesis and cancer inhibition of ovarian cancer (OC). However, lncRNAs involved in m6A regulation (LI-m6As) have never been reported in OC. Herein, we aimed to identify and validate a signature based on LI-m6A for OC. Methods RNA sequencing profiles with corresponding clinical information associated with OC and 23 m6A regulators were extracted from TCGA. The Pearson correlation coefficient (PCC) between lncRNAs and 23 m6A regulators (|PCC|> 0.4 and p < 0.01) was calculated to identify LI-m6As. The LI-m6As with significant prognostic value were screened based on univariate Cox regression analysis to construct a risk model by LASSO Cox regression. Gene Set Enrichment Analysis (GSEA) was implemented to survey the biological functions of the risk groups. Several clinicopathological characteristics were utilized to evaluate their ability to predict prognosis, and a nomogram was constructed to evaluate the accuracy of survival prediction. Besides, immune microenvironment, checkpoint, and drug sensitivity in the two risk groups were compared using comprehensive algorithms. Finally, real-time qPCR analysis and cell counting kit-8 assays were performed on an alternative lncRNA, CACNA1G-AS1. Results The training cohort involving 258 OC patients and the validation cohort involving 111 OC patients were downloaded from TCGA. According to the PCC between the m6A regulators and lncRNAs, 129 LI-m6As were obtained to perform univariate Cox regression analysis and then 10 significant prognostic LI-m6As were identified. A prognostic signature containing four LI-m6As (AC010894.3, ACAP2-IT1, CACNA1G-AS1, and UBA6-AS1) was constructed according to the LASSO Cox regression analysis of the 10 LI-m6As. The prognostic signature was validated to show completely opposite prognostic value in the two risk groups and adverse overall survival (OS) in several clinicopathological characteristics. GSEA indicated that differentially expressed genes in disparate risk groups were enriched in several tumor-related pathways. At the same time, we found significant differences in some immune cells and chemotherapeutic agents between the two groups. An alternative lncRNA, CACNA1G-AS1, was proven to be upregulated in 30 OC specimens and 3 OC cell lines relative to control. Furthermore, knockdown of CACNA1G‐AS1 was proven to restrain the multiplication capacity of OC cells. Conclusions Based on the four LI-m6As (AC010894.3, ACAP2-IT1, CACNA1G-AS1, and UBA6-AS1), the risk model we identified can independently predict the OS and therapeutic value of OC. CACNA1G‐AS1 was preliminarily proved to be a malignant lncRNA.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification and validation of lncRNAs involved in m6A regulation for patients with ovarian cancer

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The fact that the human NSUN5 CpG island promoter can be epigenetically regulated [159] may be a way environmental cues could achieve such regulation. Overall, these observations suggest that RCM1(NSUN5) and NOP2 (NSUN1) (at least in nematodes), by adjusting ribosome m 5 [12,165,166] and by ZCCHC4 on 28S/26S [12,167,168]. In nematodes, the loss of METL5 does not globally affect translation while the TE of cyp-29A3, a transcript coding for a cytochrome P450, is reduced 10fold, suggesting that ribosome 18S m 6 A methylation levels can regulate the translation of specific mRNAs [166].…”

Section: C Rrna Variations and Impact On Translationmentioning

confidence: 90%

Variations in transfer and ribosomal RNA epitranscriptomic status can adapt eukaryote translation to changing physiological and environmental conditions

2021

View full text Add to dashboard Cite

The timely reprogramming of gene expression in response to internal and external cues is essential to eukaryote development and acclimation to changing environments. Chemically modifying molecular receptors and transducers of these signals is one way to efficiently induce proper physiological responses. Post-translation modifications, regulating protein biological activities, are central to many well-known signal-responding pathways. Recently, messenger RNA (mRNA) chemical (i.e. epitranscriptomic) modifications were also shown to play a key role in these processes. In contrast, transfer RNA (tRNA) and ribosomal RNA (rRNA) chemical modifications, although critical for optimal function of the translation apparatus, and much more diverse and quantitatively important compared to mRNA modifications, were until recently considered as mainly static chemical decorations. We present here recent observations that are challenging this view and supporting the hypothesis that tRNA and rRNA modifications dynamically respond to various cell and environmental conditions and contribute to adapt translation to these conditions.

show abstract

“…However, current studies are mainly focused on the function of the METTL3-METTL14-WTAP complex in cancer, and other m6A methyltransferases may contribute to cancer initiation and maintenance by regulating RNA species- and site-specific m6A. Two studies have begun to show the oncogenic role of METTL5, an rRNA m6A methyltransferase, in breast cancer [ 152 ] and lung adenocarcinomas [ 153 ]. The function of the other rRNA m6A methyltransferase, ZCCHC4, in cancer is largely unknown.…”

Section: Discussionmentioning

confidence: 99%

N6-methyladenosine methyltransferases: functions, regulation, and clinical potential

et al. 2021

View full text Add to dashboard Cite

N6-methyladenosine (m6A) has emerged as an abundant modification throughout the transcriptome with widespread functions in protein-coding and noncoding RNAs. It affects the fates of modified RNAs, including their stability, splicing, and/or translation, and thus plays important roles in posttranscriptional regulation. To date, m6A methyltransferases have been reported to execute m6A deposition on distinct RNAs by their own or forming different complexes with additional partner proteins. In this review, we summarize the function of these m6A methyltransferases or complexes in regulating the key genes and pathways of cancer biology. We also highlight the progress in the use of m6A methyltransferases in mediating therapy resistance, including chemotherapy, targeted therapy, immunotherapy and radiotherapy. Finally, we discuss the current approaches and clinical potential of m6A methyltransferase-targeting strategies.

show abstract

Ribosome 18S m6A Methyltransferase METTL5 Promotes Translation Initiation and Breast Cancer Cell Growth

Cited by 81 publications

References 52 publications

Identification and validation of lncRNAs involved in m6A regulation for patients with ovarian cancer

Identification and validation of lncRNAs involved in m6A regulation for patients with ovarian cancer

Variations in transfer and ribosomal RNA epitranscriptomic status can adapt eukaryote translation to changing physiological and environmental conditions

N6-methyladenosine methyltransferases: functions, regulation, and clinical potential

Contact Info

Product

Resources

About