Opposing roles of miR‐294 and
            <scp>MBNL</scp>
            1/2 in shaping the gene regulatory network of embryonic stem cells

Wu, Daren; Gu, Kaili; Yu, Jian‐Cheng; Fu, Xing; Wang, Xi‑Wen; Guo, Wenting; Liao, Le‐Qi; Zhu, Hong; Zhang, Xiao‐Shan; Hui, Jingyi; Wang, Yangming

doi:10.15252/embr.201745657

Cited by 17 publications

(13 citation statements)

References 52 publications

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“…1B), while cell apoptosis was signi cantly inhibited by the knockdown of MBNL1 (Fig. 1C,D), similar to the previous study (Wu et al, 2018). These results illustrated that the cell proliferation was increased, while apoptosis was inhibited by shMBNL1 in HeLa cells.…”

Section: Resultssupporting

confidence: 89%

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MBNL1 Regulates the Expression and Alternative Splicing of Genes Enriched in Cell Adhesion and Apoptosis

Liu

Song

et al. 2021

Preprint

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Muscleblind Like Splicing Regulator 1 (MBNL1), one canonical RNA binding protein (RBP), plays important roles in the regulation of the alternative splicing (AS) on pre-mRNAs. MBNL1 has traditionally been considered involved in the pathogenesis of myotonic dystrophy. Recent researches point out that MBNL1 has an effect on cancer progress, but the underlying mechanisms are unclear. In this study, we obtained the regulated transcriptome profile of MBNL1 in HeLa cells by RNA-seq analysis. The results showed that the knockdown of MBNL1 promoted cell proliferation while inhibited apoptosis. We found 398 genes were differentially up-regulated and 277 down-regulated by MBNL1 knockdown (KD). The differentially expressed genes (DEGs) regulated by MBNL1-KD were enriched in the signal pathways of homophilic cell adhesion, apoptotic process, extracellular matrix organization and cell migration. Systematical AS analysis revealed 504 MBNL1-regulated AS events. The regulated alternative splicing genes (RASGs) were enriched in the signal pathways of apoptotic signaling pathway, positive regulation of apoptotic process, adherent junction, fatty acid elongation and DNA repair. In summary, our results demonstrate that the knockdown of MBNL1 have significant effects on cell proliferation and apoptosis by regulating the expression and alternative splicing of associated genes, illustrating the possible molecular mechanisms of MBNL1 in cancer pathogenesis and progression and other diseases.

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Section: Resultssupporting

confidence: 89%

“…Some research have pointed out that MBNL1 may play an important role in the cell apoptosis (Wu et al, 2018;Sznajder et al, 2020). They pointed out that MBNL1 overexpression signi cantly decreased the proliferation rate and increased apoptosis (Wu et al, 2018). Our results consist with previous studies on cell proliferation and apoptosis.…”

Section: Discussionsupporting

confidence: 91%

MBNL1 Regulates the Expression and Alternative Splicing of Genes Enriched in Cell Adhesion and Apoptosis

Liu

Song

et al. 2021

Preprint

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“…The latter was underlain by high-throughput analysis of structural context of ADAR-edited regions which co-occurred with alternative events [ 251 ]. The structure switch of RNA regulatory elements was found decisive for the AS coordination by several splicing factors such as hnRNP C [ 50 ], hnRNP G [ 120 ], and hnRNP A2/B1 [ 252 ]. Recent findings report that binding of ADAR itself to dsRNA regions formed between GA-rich sequences and Py-tract governs AS through either sterically precluding access of U2AF65 to nearby Py-tract or by masking the splice sites [ 137 , 140 ].…”

Section: Mechanism Of Alternative Splicing Regulation By Rna Strucmentioning

confidence: 99%

Intrinsic Regulatory Role of RNA Structural Arrangement in Alternative Splicing Control

Taylor

Sobczak

2020

IJMS

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Alternative splicing is a highly sophisticated process, playing a significant role in posttranscriptional gene expression and underlying the diversity and complexity of organisms. Its regulation is multilayered, including an intrinsic role of RNA structural arrangement which undergoes time- and tissue-specific alterations. In this review, we describe the principles of RNA structural arrangement and briefly decipher its cis- and trans-acting cellular modulators which serve as crucial determinants of biological functionality of the RNA structure. Subsequently, we engage in a discussion about the RNA structure-mediated mechanisms of alternative splicing regulation. On one hand, the impairment of formation of optimal RNA structures may have critical consequences for the splicing outcome and further contribute to understanding the pathomechanism of severe disorders. On the other hand, the structural aspects of RNA became significant features taken into consideration in the endeavor of finding potential therapeutic treatments. Both aspects have been addressed by us emphasizing the importance of ongoing studies in both fields.

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“…Importantly, MBNL regulates miRNA biogenesis [ 78 ] and circRNA formation [ 101 ]. Moreover, extensive crosstalk between miRNAs and splicing factors in regulating alternative splicing and gene expression program, during development and cellular differentiation, was reported [ 102 ]. Because individual miRNAs can target multiple miRNAs [ 23 ] and different RNA regulatory processes are interrelated and overlapping, we can expect that ceRNA networking and miRNA sponging may play an important role in the pathogenesis of both DMs.…”

Section: Current Understanding Of the Activity Of Cernas In Dms And Directions For Further Researchmentioning

confidence: 99%

Regulatory Potential of Competing Endogenous RNAs in Myotonic Dystrophies

Kościańska

Kozłowska

Fiszer

2021

IJMS

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Non-coding RNAs (ncRNAs) have been reported to be implicated in cell fate determination and various human diseases. All ncRNA molecules are emerging as key regulators of diverse cellular processes; however, little is known about the regulatory interaction among these various classes of RNAs. It has been proposed that the large-scale regulatory network across the whole transcriptome is mediated by competing endogenous RNA (ceRNA) activity attributed to both protein-coding and ncRNAs. ceRNAs are considered to be natural sponges of miRNAs that can influence the expression and availability of multiple miRNAs and, consequently, the global mRNA and protein levels. In this review, we summarize the current understanding of the role of ncRNAs in two neuromuscular diseases, myotonic dystrophy type 1 and 2 (DM1 and DM2), and the involvement of expanded CUG and CCUG repeat-containing transcripts in miRNA-mediated RNA crosstalk. More specifically, we discuss the possibility that long repeat tracts present in mutant transcripts can be potent miRNA sponges and may affect ceRNA crosstalk in these diseases. Moreover, we highlight practical information related to innovative disease modelling and studying RNA regulatory networks in cells. Extending knowledge of gene regulation by ncRNAs, and of complex regulatory ceRNA networks in DM1 and DM2, will help to address many questions pertinent to pathogenesis and treatment of these disorders; it may also help to better understand general rules of gene expression and to discover new rules of gene control.

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Opposing roles of miR‐294 and MBNL 1/2 in shaping the gene regulatory network of embryonic stem cells

Cited by 17 publications

References 52 publications

MBNL1 Regulates the Expression and Alternative Splicing of Genes Enriched in Cell Adhesion and Apoptosis

MBNL1 Regulates the Expression and Alternative Splicing of Genes Enriched in Cell Adhesion and Apoptosis

Intrinsic Regulatory Role of RNA Structural Arrangement in Alternative Splicing Control

Regulatory Potential of Competing Endogenous RNAs in Myotonic Dystrophies

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