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Long non-coding RNA-polycomb intimate rendezvous.

ABSTRACT: The interaction between polycomb-repressive complexes 1/2 (PRC1/2) and long non-coding RNA (lncRNA), such as the X inactive specific transcript Xist and the HOX transcript antisense RNA (HOTAIR), has been the subject of intense debate. While cross-linking, immuno-precipitation and super-resolution microscopy argue against direct interaction of Polycomb with some lncRNAs, there is increasing evidence supporting the ability of both PRC1 and PRC2 to functionally associate with RNA. Recent data indicate that these interactions are in most cases spurious, but nonetheless crucial for a number of cellular activities. In this review, we suggest that while PRC1/2 recruitment by HOTAIR might be direct, in the case of Xist, it might occur indirectly and, at least in part, through the process of liquid-liquid phase separation. We present recent models of lncRNA-mediated PRC1/2 recruitment to their targets and describe potential RNA-mediated roles in the three-dimensional organization of the nucleus.

SUBMITTER: Cerase A

PROVIDER: S-EPMC7536065 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Long non-coding RNA-polycomb intimate rendezvous.

Cerase Andrea A Tartaglia Gian Gaetano GG

Open biology 20200909 9

The interaction between polycomb-repressive complexes 1/2 (PRC1/2) and long non-coding RNA (lncRNA), such as the X inactive specific transcript <i>Xist</i> and the HOX transcript antisense RNA (HOTAIR), has been the subject of intense debate. While cross-linking, immuno-precipitation and super-resolution microscopy argue against direct interaction of Polycomb with some lncRNAs, there is increasing evidence supporting the ability of both PRC1 and PRC2 to functionally associate with RNA. Recent da ...[more]

PMID: 32898472

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Project description:Neuroblastoma (NB) is an embryonal tumor with various clinical presentations and behaviors. Several genomic alterations has been well-studied in NB, among which genomic amplification of MYCN oncogene, is a strong prognostic biomarker with worsens outcome. Long noncoding RNAs (lncRNAs), constitute major proportion of the cellular transcripts with no coding capacity. One of their function is to guide transcription factors to the target genes and facilitate gene expression. However, relative contribution of lncRNA and MYCN to the advanced NB has remained unclear. Herein, by applying a network-based integrative analysis on MYCN amplified and MYCN nonamplified lncRNA expression profile from both RNA-seq and microarray platform, we identified lncRNA, SNHG1 to be differentially expressed and strongly correlated with MYCN in MYCN-amplified NB. The expression of SNHG1 was validated by RT-qPCR in NB cell lines. Survival analysis revealed that higher expression of SNHG1 significantly associates with poor patient survival. Moreover, knockdown of MYCN in MYCN-amplified NB cell lines inhibited SNHG1 expression. Furthermore, to unravel the role of SNHG1 in NB, we extracted SNHG1-interacting proteins by RNA-protein pull down assay coupled with doi:10.6342/NTU201701980 ! ! VI liquid chromatography-tandem mass spectrometry (LC-MS/MS). We identified 27 SNHG1-interacting proteins in common from three NB cell lines. However, only three SNHG1-interacting proteins, MATR3, YBX1 and HHRNPL have binding site detected by DeepBind motif analysis. Western blot confirms interaction of MATR3 with SNHG1. Additionally, we further validated the direct interaction between MATR3 and SNHG1 by RNA-immunoprecipation (IP). MATR3 is known to be involved in RNA transport and stabilization. Therefore, we proposed that MATR3 after interacting with SNHG1 might help in SNHG1 transcription and stabilization. In conclusion, our study unveils that SNHG1 could be a prognostic marker for high-risk NB and possibly stabilized by MATR3. Our results might provide future directions for the development of therapeutic strategies against high-risk NB.

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Long non-coding RNA-polycomb intimate rendezvous.

Publications

Long non-coding RNA-polycomb intimate rendezvous.

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