Nuclear m6A reader YTHDC1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos

Chen, Chuan; Liu, Wenqiang; Guo, Jiayin; Liu, Yuanyuan; Liu, Xuelian; Liu, Jun; Dou, Xiaoyang; Le, Rongrong; Huang, Yixin; Li, Chong; Yang, Lingyue; Kou, Xiaochen; Zhao, Yanhong; Wu, You; Chen, Jiayu; Wang, Hong; Shen, Bin; Gao, Yawei; Gao, Shaorong

doi:10.1007/s13238-021-00837-8

Cited by 97 publications

(92 citation statements)

References 50 publications

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“…This manner of transcript inhibition can be used by mouse embryonic cells to repress LINE1 and other retrotransposons (IAP, ERVK, etc.) [161,162]. A lack of YTHDC1, a factor that initiates silencing by recognizing N6-methyladenosine modification and transcript binding, leads to the transition to the 2-cell embryo stage [161,162].…”

Section: Regulation Of L1 In the Early Stages Of Embryogenesismentioning

confidence: 99%

“…[161,162]. A lack of YTHDC1, a factor that initiates silencing by recognizing N6-methyladenosine modification and transcript binding, leads to the transition to the 2-cell embryo stage [161,162]. Post-transcriptional degradation of L1 in early embryos can occur due to the nuclear exosome targeting (NEXT) complex, the central factor of which is Zcchc8 [131].…”

Section: Regulation Of L1 In the Early Stages Of Embryogenesismentioning

confidence: 99%

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Factors Regulating the Activity of LINE1 Retrotransposons

Protasova

Andreeva

Rogaev

2021

Genes

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LINE-1 (L1) is a class of autonomous mobile genetic elements that form somatic mosaicisms in various tissues of the organism. The activity of L1 retrotransposons is strictly controlled by many factors in somatic and germ cells at all stages of ontogenesis. Alteration of L1 activity was noted in a number of diseases: in neuropsychiatric and autoimmune diseases, as well as in various forms of cancer. Altered activity of L1 retrotransposons for some pathologies is associated with epigenetic changes and defects in the genes involved in their repression. This review discusses the molecular genetic mechanisms of the retrotransposition and regulation of the activity of L1 elements. The contribution of various factors controlling the expression and distribution of L1 elements in the genome occurs at all stages of the retrotransposition. The regulation of L1 elements at the transcriptional, post-transcriptional and integration into the genome stages is described in detail. Finally, this review also focuses on the evolutionary aspects of L1 accumulation and their interplay with the host regulation system.

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Section: Regulation Of L1 In the Early Stages Of Embryogenesismentioning

confidence: 99%

Section: Regulation Of L1 In the Early Stages Of Embryogenesismentioning

confidence: 99%

Factors Regulating the Activity of LINE1 Retrotransposons

Protasova

Andreeva

Rogaev

2021

Genes

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“…In the absence of YTHDC1, m6A-marked LINE1 was recruited on the Dux1 locus where it mediated chromatin repression [ 80 ]. These findings were confirmed in a follow up study by Chen et al, who found that m6A-marked LINE1 can complex with Nucleolin (NCL) to inhibit the re-expression of TE, controlling the execution of the 2C-like state program [ 81 ] ( Figure 1 C).…”

Section: Transposable Elements Rna Modifications and Chromatin Organi...mentioning

confidence: 57%

“…Three studies have recently reported the regulatory activity of m6A over LINE1 in mouse ES cells [ 79 , 80 , 81 ]. The first study [ 79 ], which looked at genome-wide regulation of chromatin accessibility by m6A ( Figure 1 A), found the robust enrichment of m6A at chromatin-associated repetitive RNAs (carRNAs) of the mESc genome.…”

Section: Transposable Elements Rna Modifications and Chromatin Organi...mentioning

confidence: 99%

Driving Chromatin Organisation through N6-methyladenosine Modification of RNA: What Do We Know and What Lies Ahead?

Selmi

Lanzuolo

2022

Genes

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In recent years, there has been an increase in research efforts surrounding RNA modification thanks to key breakthroughs in NGS-based whole transcriptome mapping methods. More than 100 modifications have been reported in RNAs, and some have been mapped at single-nucleotide resolution in the mammalian transcriptome. This has opened new research avenues in fields such as neurobiology, developmental biology, and oncology, among others. To date, we know that the RNA modification machinery finely tunes many diverse mechanisms involved in RNA processing and translation to regulate gene expression. However, it appears obvious to the research community that we have only just begun the process of understanding the several functions of the dynamic web of RNA modification, or the “epitranscriptome”. To expand the data generated so far, recently published studies revealed a dual role for N6-methyladenosine (m6A), the most abundant mRNA modification, in driving both chromatin dynamics and transcriptional output. These studies showed that the m6A-modified, chromatin-associated RNAs could act as molecular docks, recruiting histone modification proteins and thus contributing to the regulation of local chromatin structure. Here, we review these latest exciting findings and outline outstanding research questions whose answers will help to elucidate the biological relevance of the m6A modification of chromatin-associated RNAs in mammalian cells.

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“…These highthroughput experimental data provide a special opportunity for us to explore the interactions between transposon-derived RNAs and chromatin for the understanding of the potential trans-regulatory function of these transposon RNAs. Researchers initiated to utilize the RNA-chromatin interaction data for the discovery that transposon RNAs modulate the process of heterochromatin organization (Hao et al 2020;Chen et al 2021;Liu et al 2021). In this study, we performed a high-throughput proximity MARGI experiment in E14 cells and interpreted the roles of transposon RNAs from the perspective of RNA trans-regulation on gene transcription in embryonic stem cells (ESCs).…”

Section: Introductionmentioning

confidence: 99%

Chromatin-interacting transposon RNAs linking to the core trans-inhibition circuitry for embryonic stem cell identity

Ren

Zheng

2021

Preprint

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Transposable DNA sequences constitute more than half of the human and mouse genomes. A large number of non-coding RNAs, named as transposon RNAs, are derived from these transposable elements. The cis-regulatory function of transposable DNA elements, such as LINE-1 and Alu has been largely explored. But the biological roles of transposon RNAs aren't well understood. Here, investigations of RNA-chromatin interactions provide us with comprehensive evidence that specific families of transposon RNAs play roles in trans-regulation linking to the core inhibition circuitry for embryonic stem cell identity. Alternative modes of the RNA-DNA hybrid duplex and protein-recruited RNA scaffold are required for the regulatory activities of transposon RNAs. LINE-1 RNAs co-locating with KAP1 form a negative feedback loop stabilizing the transcription of LINE-1 DNA elements via RNA-DNA hybrids. In another way LINE-1 RNAs, together with the reprogramming three factors and Polycomb repressive complexes, participate in the inhibition on dozens of differentiation-relative genes.

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Nuclear m6A reader YTHDC1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos

Cited by 97 publications

References 50 publications

Factors Regulating the Activity of LINE1 Retrotransposons

Factors Regulating the Activity of LINE1 Retrotransposons

Driving Chromatin Organisation through N6-methyladenosine Modification of RNA: What Do We Know and What Lies Ahead?

Chromatin-interacting transposon RNAs linking to the core trans-inhibition circuitry for embryonic stem cell identity

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