Chromatin modifier HUSH co-operates with RNA decay factor NEXT to restrict transposable element expression

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Chromatin modifier HUSH co-operates with RNA decay factor NEXT to restrict transposable element expression. / Garland, William; Müller, Iris; Wu, Mengjun; Schmid, Manfred; Imamura, Katsutoshi; Rib, Leonor; Sandelin, Albin; Helin, Kristian; Jensen, Torben Heick.

In: Molecular Cell, Vol. 82, No. 9, 2022, p. 1691-1707.e8.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Garland, W, Müller, I, Wu, M, Schmid, M, Imamura, K, Rib, L, Sandelin, A, Helin, K & Jensen, TH 2022, 'Chromatin modifier HUSH co-operates with RNA decay factor NEXT to restrict transposable element expression', Molecular Cell, vol. 82, no. 9, pp. 1691-1707.e8. https://doi.org/10.1016/j.molcel.2022.03.004

APA

Garland, W., Müller, I., Wu, M., Schmid, M., Imamura, K., Rib, L., Sandelin, A., Helin, K., & Jensen, T. H. (2022). Chromatin modifier HUSH co-operates with RNA decay factor NEXT to restrict transposable element expression. Molecular Cell, 82(9), 1691-1707.e8. https://doi.org/10.1016/j.molcel.2022.03.004

Vancouver

Garland W, Müller I, Wu M, Schmid M, Imamura K, Rib L et al. Chromatin modifier HUSH co-operates with RNA decay factor NEXT to restrict transposable element expression. Molecular Cell. 2022;82(9):1691-1707.e8. https://doi.org/10.1016/j.molcel.2022.03.004

Author

Garland, William ; Müller, Iris ; Wu, Mengjun ; Schmid, Manfred ; Imamura, Katsutoshi ; Rib, Leonor ; Sandelin, Albin ; Helin, Kristian ; Jensen, Torben Heick. / Chromatin modifier HUSH co-operates with RNA decay factor NEXT to restrict transposable element expression. In: Molecular Cell. 2022 ; Vol. 82, No. 9. pp. 1691-1707.e8.

Bibtex

@article{6cd74e2c021a42a7ad0718afdd312498,
title = "Chromatin modifier HUSH co-operates with RNA decay factor NEXT to restrict transposable element expression",
abstract = "Transposable elements (TEs) are widespread genetic parasites known to be kept under tight transcriptional control. Here, we describe a functional connection between the mouse-orthologous “nuclear exosome targeting” (NEXT) and “human silencing hub” (HUSH) complexes, involved in nuclear RNA decay and the epigenetic silencing of TEs, respectively. Knocking out the NEXT component ZCCHC8 in embryonic stem cells results in elevated TE RNA levels. We identify a physical interaction between ZCCHC8 and the MPP8 protein of HUSH and establish that HUSH recruits NEXT to chromatin at MPP8-bound TE loci. However, while NEXT and HUSH both dampen TE RNA expression, their activities predominantly affect shorter non-polyadenylated and full-length polyadenylated transcripts, respectively. Indeed, our data suggest that the repressive action of HUSH promotes a condition favoring NEXT RNA decay activity. In this way, transcriptional and post-transcriptional machineries synergize to suppress the genotoxic potential of TE RNAs.",
keywords = "HUSH complex, NEXT complex, retrotransposons, RNA decay, RNA exosome, transposable elements",
author = "William Garland and Iris M{\"u}ller and Mengjun Wu and Manfred Schmid and Katsutoshi Imamura and Leonor Rib and Albin Sandelin and Kristian Helin and Jensen, {Torben Heick}",
note = "Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
doi = "10.1016/j.molcel.2022.03.004",
language = "English",
volume = "82",
pages = "1691--1707.e8",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "9",

}

RIS

TY - JOUR

T1 - Chromatin modifier HUSH co-operates with RNA decay factor NEXT to restrict transposable element expression

AU - Garland, William

AU - Müller, Iris

AU - Wu, Mengjun

AU - Schmid, Manfred

AU - Imamura, Katsutoshi

AU - Rib, Leonor

AU - Sandelin, Albin

AU - Helin, Kristian

AU - Jensen, Torben Heick

N1 - Publisher Copyright: © 2022 The Authors

PY - 2022

Y1 - 2022

N2 - Transposable elements (TEs) are widespread genetic parasites known to be kept under tight transcriptional control. Here, we describe a functional connection between the mouse-orthologous “nuclear exosome targeting” (NEXT) and “human silencing hub” (HUSH) complexes, involved in nuclear RNA decay and the epigenetic silencing of TEs, respectively. Knocking out the NEXT component ZCCHC8 in embryonic stem cells results in elevated TE RNA levels. We identify a physical interaction between ZCCHC8 and the MPP8 protein of HUSH and establish that HUSH recruits NEXT to chromatin at MPP8-bound TE loci. However, while NEXT and HUSH both dampen TE RNA expression, their activities predominantly affect shorter non-polyadenylated and full-length polyadenylated transcripts, respectively. Indeed, our data suggest that the repressive action of HUSH promotes a condition favoring NEXT RNA decay activity. In this way, transcriptional and post-transcriptional machineries synergize to suppress the genotoxic potential of TE RNAs.

AB - Transposable elements (TEs) are widespread genetic parasites known to be kept under tight transcriptional control. Here, we describe a functional connection between the mouse-orthologous “nuclear exosome targeting” (NEXT) and “human silencing hub” (HUSH) complexes, involved in nuclear RNA decay and the epigenetic silencing of TEs, respectively. Knocking out the NEXT component ZCCHC8 in embryonic stem cells results in elevated TE RNA levels. We identify a physical interaction between ZCCHC8 and the MPP8 protein of HUSH and establish that HUSH recruits NEXT to chromatin at MPP8-bound TE loci. However, while NEXT and HUSH both dampen TE RNA expression, their activities predominantly affect shorter non-polyadenylated and full-length polyadenylated transcripts, respectively. Indeed, our data suggest that the repressive action of HUSH promotes a condition favoring NEXT RNA decay activity. In this way, transcriptional and post-transcriptional machineries synergize to suppress the genotoxic potential of TE RNAs.

KW - HUSH complex

KW - NEXT complex

KW - retrotransposons

KW - RNA decay

KW - RNA exosome

KW - transposable elements

U2 - 10.1016/j.molcel.2022.03.004

DO - 10.1016/j.molcel.2022.03.004

M3 - Journal article

C2 - 35349793

AN - SCOPUS:85129247825

VL - 82

SP - 1691-1707.e8

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 9

ER -

ID: 307329428