Unusual semi‐extractability as a hallmark of nuclear body‐associated architectural noncoding <scp>RNA</scp>s

Chujo, Takeshi; Yamazaki, Tomohiro; Kawaguchi, Tetsuya; Kurosaka, Satoshi; Takumi, Toru; Nakagawa, Shinichi; Hirose, Tetsuro

doi:10.15252/embj.201695848

Cited by 109 publications

(152 citation statements)

References 57 publications

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“…In cells residing in other phases of the cell cycle, NEAT1_2 is the only isoform present and therefore PS are, by and large, NEAT1_1-free in these cells. Our data is, however, in line with previous quantifications of NEAT1_1 RNA levels, indicating that, on the basis of stoichiometry, NEAT1_1 transcripts are not likely to locate to PS, or at least not in significant amounts (Chujo et al 2017;Li et al 2017). Our data also suggest that PS can be assembled in the absence of NEAT1_1.…”

Section: Discussionsupporting

confidence: 91%

The lncRNA NEAT1_1 is dispensable for normal tissue homeostasis and cancer cell growth

Adriaens¹,

Rambow²,

Bervoets³

et al. 2019

Preprint

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NEAT1 is one of the most studied lncRNAs, in part because its silencing in mice causes defects in mammary gland development and corpus luteum formation, and protects them from skin cancer development. Moreover, depleting NEAT1 in established cancer cell lines reduces growth and sensitizes cells to DNA damaging agents. However, NEAT1 produces two isoforms and because the short isoform, NEAT1_1, completely overlaps the 5' part of the long NEAT1_2 isoform, the respective contributions of each of the isoforms to these phenotypes has remained unclear. Whereas NEAT1_1 is highly expressed in most tissues, NEAT1_2 is the central architectural component of paraspeckles, which are nuclear bodies that assemble in specific tissues and cells exposed to various forms of stress. Using dual RNA-FISH to detect both NEAT1_1 outside of paraspeckles and NEAT1_2/NEAT1 inside this nuclear body, we report herein that NEAT1_1 levels are dynamically regulated during the cell cycle and targeted for degradation by the nuclear RNA exosome. Unexpectedly, however, cancer cells engineered to lack NEAT1_1, but not NEAT1_2, do not exhibit cell cycle defects. Moreover, Neat1_1-specific knockout mice do not exhibit the phenotypes observed in Neat1-deficient mice. We propose that NEAT1 functions are mainly, if not exclusively, attributable to NEAT1_2 and, by extension, to paraspeckles.

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Section: Discussionsupporting

confidence: 91%

The lncRNA NEAT1_1 is dispensable for normal tissue homeostasis and cancer cell growth

Adriaens¹,

Rambow²,

Bervoets³

et al. 2019

Preprint

Self Cite

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show abstract

“…However, BRG1 does not require its ATPase catalytic site for this structural role. In terms of stoichiometry, recent quantitative analysis revealed the presence of ~50 NEAT1_2 molecules in a single paraspeckle particle [23], but the stoichiometry of different paraspeckle proteins is yet to be determined.…”

Section: How Do Paraspeckles Form?mentioning

confidence: 99%

Paraspeckles: Where Long Noncoding RNA Meets Phase Separation

Fox

Nakagawa

Hirose

et al. 2018

Trends in Biochemical Sciences

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346

338

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Long noncoding RNA (lncRNA) molecules are some of the newest and least understood players in gene regulation. Hence, we need good model systems with well-defined RNA and protein components. One such system is paraspeckles - protein-rich nuclear organelles built around a specific lncRNA scaffold. New discoveries show how paraspeckles are formed through multiple RNA-protein and protein-protein interactions, some of which involve extensive polymerization, and others with multivalent interactions driving phase separation. Once formed, paraspeckles influence gene regulation through sequestration of component proteins and RNAs, with subsequent depletion in other compartments. Here we focus on the dual aspects of paraspeckle structure and function, revealing an emerging role for these dynamic bodies in a multitude of cellular settings.

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“…Most of these studies are performed in cancer cell lines. For example, as of March 2018, there are at least 17 studies reporting ceRNA activity of PVT1 , a moderately abundant lncRNA, that is almost exclusively nuclear , and therefore not expected to effectively bind miRNAs. Strikingly, these studies collectively implicate 10 different miRNAs as being ‘sponged’ by PVT1.…”

Section: Regulation Of Small Rna Activity By Long Noncoding Rnasmentioning

confidence: 99%

Interactions between short and long noncoding RNAs

Ulitsky

2018

FEBS Letters

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It is now evident that noncoding RNAs play key roles in regulatory networks determining cell fate and behavior, in a myriad of different conditions, and across all species. Among these noncoding RNAs are short RNAs, such as MicroRNAs, snoRNAs, and Piwi-interacting RNAs, and the functions of those are relatively well understood. Other noncoding RNAs are longer, and their modes of action and functions are also increasingly explored and deciphered. Short RNAs and long noncoding RNAs (lncRNAs) interact with each other with reciprocal consequences for their fates and functions. LncRNAs serve as precursors for many types of small RNAs and, therefore, the pathways for small RNA biogenesis can impinge upon the fate of lncRNAs. In addition, lncRNA expression can be repressed by small RNAs, and lncRNAs can affect small RNA activity and abundance through competition for binding or by triggering small RNA degradation. Here, I review the known types of interactions between small and long RNAs, discuss their outcomes, and bring representative examples from studies in mammals.

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Unusual semi‐extractability as a hallmark of nuclear body‐associated architectural noncoding RNAs

Cited by 109 publications

References 57 publications

The lncRNA NEAT1_1 is dispensable for normal tissue homeostasis and cancer cell growth

The lncRNA NEAT1_1 is dispensable for normal tissue homeostasis and cancer cell growth

Paraspeckles: Where Long Noncoding RNA Meets Phase Separation

Interactions between short and long noncoding RNAs

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