Beyond rRNA: nucleolar transcription generates a complex network of RNAs with multiple roles in maintaining cellular homeostasis

Feng, Shuang; Manley, James L.

doi:10.1101/gad.349969.122

Cited by 13 publications

(8 citation statements)

References 90 publications

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“…5D). Many RBPs display stress-induced nucleolar relocalisation (Mamontova et al 2021;Feng and Manley 2022). We provide evidence for diNARinduced nucleolar R-loops as anchor for nucleolar NONO.…”

Section: Discussionsupporting

confidence: 50%

“…Non-ribosomal, nucleolar transcripts maintain homeostasis by sequestration of RBPs (Mamontova et al 2021;Feng and Manley 2022). Intriguingly, carboxy-terminal domain ser-2 phosphorylated RNA polymerase II (CTD S2P) synthesises antisense intergenic ncRNA (asincRNA) on nucleolar chromatin to regulate RNA polymerase I (RNAPI) in unperturbed cells (Abraham et al 2020).…”

Section: Rnapii Produces Dna Damage-induced Nucleolar Transcripts At ...mentioning

confidence: 99%

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Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts

Trifault

Mamontova

Cossa

et al. 2023

Preprint

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RNA-binding proteins (RBPs) stimulate the DNA damage response (DDR). The RBP NONO marks nuclear paraspeckles in unperturbed cells and undergoes poorly understood re-localisation to the nucleolus upon induction of DNA double-strand breaks (DSBs). Here we show that treatment with the topoisomerase-II inhibitor etoposide stimulates the production of RNA polymerase II-dependent, DNA damage-induced nucleolar antisense RNAs (diNARs) in human cells. diNARs originate from the nucleolar intergenic spacer and tether NONO to the nucleolus via its RRM1 domain. NONO occupancy at protein-coding gene promoters is reduced by etoposide, which attenuates pre-mRNA synthesis, enhances NONO binding to pre-mRNA transcripts and is accompanied by nucleolar detention of such transcripts. The depletion or mutation of NONO interferes with detention and prolongs DSB signaling. Together, we describe a nucleolar DDR pathway that shields NONO and aberrant transcripts from DSBs to promote DNA repair.

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Section: Discussionsupporting

confidence: 50%

Section: Rnapii Produces Dna Damage-induced Nucleolar Transcripts At ...mentioning

confidence: 99%

Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts

Trifault

Mamontova

Cossa

et al. 2023

Preprint

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“…Several transcription termination sequences after the 3’ETS terminate Pol I transcription [ 24 , 36 ]. Other than the aforementioned promoters, enhancers, and transcription terminators, the IGS sequences also contain simple repeats, transposable elements, and non-coding sequences that are transcribed by Pol II [ 18 ], reviewed in [ 37 ].…”

Section: Introduction: Rna Polymerase I Is An Essential Enzyme For Ri...mentioning

confidence: 99%

Regulation of RNA Polymerase I Stability and Function

Pitts

Laiho

2022

Cancers

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RNA polymerase I is a highly processive enzyme with fast initiation and elongation rates. The structure of Pol I, with its in-built RNA cleavage ability and incorporation of subunits homologous to transcription factors, enables it to quickly and efficiently synthesize the enormous amount of rRNA required for ribosome biogenesis. Each step of Pol I transcription is carefully controlled. However, cancers have highjacked these control points to switch the enzyme, and its transcription, on permanently. While this provides an exceptional benefit to cancer cells, it also creates a potential cancer therapeutic vulnerability. We review the current research on the regulation of Pol I transcription, and we discuss chemical biology efforts to develop new targeted agents against this process. Lastly, we highlight challenges that have arisen from the introduction of agents with promiscuous mechanisms of action and provide examples of agents with specificity and selectivity against Pol I.

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“…Besides serving as platform for ribosome assembly, nucleolus acts as a central hub in mediating multiple events including DNA damage repair, stress response, apoptosis, and chromatin regulation [38,57,58]. Recent studies highlight the interaction of nucleolus with repressive chromatin domains [59,60].…”

Section: Discussionmentioning

confidence: 99%

Paralog-dependent Specialization of Paf1C subunit, Ctr9, for Sex Chromosome Gene Regulation and Male Germline Differentiation in Drosophila

Kai,

Zheng,

Iki

2024

Preprint

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Testis-specific gene regulatory mechanisms govern the differentiation of germ cells into mature sperms. However, the molecular underpinnings are not fully elucidated. Here, we show the subunits forming Polymerase Associated Factor 1 Complex (Paf1C), a transcription regulator conserved across eukaryotes, have their individual paralogs predominantly expressed in Drosophila testes. One of these, namely, Ctr9 paralog enriched in testes (Ctr9t) was found to play a critical and nonredundant role in post-meiotic spermatid differentiation and male fertility in D. melanogaster. A proximity proteome analysis provides evidence that Ctr9t forms complexes with other paralog members. We show endogenous Ctr9t is expressed in germ cells at spermatocyte stages, accumulating in a distinct compartment within the nucleolus. There, Ctr9t co-localizes with Spermatocyte arrest (Sa), a testis-specific paralog of TATA-binding protein (TBP)-associated factor 8 (TAF8). We further demonstrate that ctr9t function is crucial for maintaining Sa in the nucleolus, but not vice versa. Transcriptome profiling reveals that Ctr9t acts as an activator for the set of male fertility genes on Y chromosome, but it also acts as a global repressor of X chromosome genes. Collectively, our results shed light on the nucleolus-associated, paralog-dependent regulation of gene expression from sex chromosomes, which ensures the terminal differentiation of male germ cells.

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Beyond rRNA: nucleolar transcription generates a complex network of RNAs with multiple roles in maintaining cellular homeostasis

Cited by 13 publications

References 90 publications

Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts

Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts

Regulation of RNA Polymerase I Stability and Function

Paralog-dependent Specialization of Paf1C subunit, Ctr9, for Sex Chromosome Gene Regulation and Male Germline Differentiation in Drosophila

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