rRNA transcription is integral to phase separation and maintenance of nucleolar structure.
Transcription of ribosomal RNA (rRNA) by RNA Polymerase (Pol) I in the nucleolus is necessary for ribosome biogenesis, which is intimately tied to cell growth and proliferation. Perturbation of ribosome biogenesis results in tissue specific disorders termed ribosomopathies in association with altera...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-08-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010854&type=printable |
| _version_ | 1797667866650083328 |
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| author | Soma Dash Maureen C Lamb Jeffrey J Lange Mary C McKinney Dai Tsuchiya Fengli Guo Xia Zhao Timothy J Corbin MaryEllen Kirkman Kym Delventhal Emma L Moore Sean McKinney Rita Shiang Paul A Trainor |
| author_facet | Soma Dash Maureen C Lamb Jeffrey J Lange Mary C McKinney Dai Tsuchiya Fengli Guo Xia Zhao Timothy J Corbin MaryEllen Kirkman Kym Delventhal Emma L Moore Sean McKinney Rita Shiang Paul A Trainor |
| author_sort | Soma Dash |
| collection | DOAJ |
| description | Transcription of ribosomal RNA (rRNA) by RNA Polymerase (Pol) I in the nucleolus is necessary for ribosome biogenesis, which is intimately tied to cell growth and proliferation. Perturbation of ribosome biogenesis results in tissue specific disorders termed ribosomopathies in association with alterations in nucleolar structure. However, how rRNA transcription and ribosome biogenesis regulate nucleolar structure during normal development and in the pathogenesis of disease remains poorly understood. Here we show that homozygous null mutations in Pol I subunits required for rRNA transcription and ribosome biogenesis lead to preimplantation lethality. Moreover, we discovered that Polr1a-/-, Polr1b-/-, Polr1c-/- and Polr1d-/- mutants exhibit defects in the structure of their nucleoli, as evidenced by a decrease in number of nucleolar precursor bodies and a concomitant increase in nucleolar volume, which results in a single condensed nucleolus. Pharmacological inhibition of Pol I in preimplantation and midgestation embryos, as well as in hiPSCs, similarly results in a single condensed nucleolus or fragmented nucleoli. We find that when Pol I function and rRNA transcription is inhibited, the viscosity of the granular compartment of the nucleolus increases, which disrupts its phase separation properties, leading to a single condensed nucleolus. However, if a cell progresses through mitosis, the absence of rRNA transcription prevents reassembly of the nucleolus and manifests as fragmented nucleoli. Taken together, our data suggests that Pol I function and rRNA transcription are required for maintaining nucleolar structure and integrity during development and in the pathogenesis of disease. |
| first_indexed | 2024-03-11T20:20:46Z |
| format | Article |
| id | doaj.art-c037fb36df1941e8ad84f0aefebb0c85 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-03-11T20:20:46Z |
| publishDate | 2023-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-c037fb36df1941e8ad84f0aefebb0c852023-10-03T05:31:11ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042023-08-01198e101085410.1371/journal.pgen.1010854rRNA transcription is integral to phase separation and maintenance of nucleolar structure.Soma DashMaureen C LambJeffrey J LangeMary C McKinneyDai TsuchiyaFengli GuoXia ZhaoTimothy J CorbinMaryEllen KirkmanKym DelventhalEmma L MooreSean McKinneyRita ShiangPaul A TrainorTranscription of ribosomal RNA (rRNA) by RNA Polymerase (Pol) I in the nucleolus is necessary for ribosome biogenesis, which is intimately tied to cell growth and proliferation. Perturbation of ribosome biogenesis results in tissue specific disorders termed ribosomopathies in association with alterations in nucleolar structure. However, how rRNA transcription and ribosome biogenesis regulate nucleolar structure during normal development and in the pathogenesis of disease remains poorly understood. Here we show that homozygous null mutations in Pol I subunits required for rRNA transcription and ribosome biogenesis lead to preimplantation lethality. Moreover, we discovered that Polr1a-/-, Polr1b-/-, Polr1c-/- and Polr1d-/- mutants exhibit defects in the structure of their nucleoli, as evidenced by a decrease in number of nucleolar precursor bodies and a concomitant increase in nucleolar volume, which results in a single condensed nucleolus. Pharmacological inhibition of Pol I in preimplantation and midgestation embryos, as well as in hiPSCs, similarly results in a single condensed nucleolus or fragmented nucleoli. We find that when Pol I function and rRNA transcription is inhibited, the viscosity of the granular compartment of the nucleolus increases, which disrupts its phase separation properties, leading to a single condensed nucleolus. However, if a cell progresses through mitosis, the absence of rRNA transcription prevents reassembly of the nucleolus and manifests as fragmented nucleoli. Taken together, our data suggests that Pol I function and rRNA transcription are required for maintaining nucleolar structure and integrity during development and in the pathogenesis of disease.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010854&type=printable |
| spellingShingle | Soma Dash Maureen C Lamb Jeffrey J Lange Mary C McKinney Dai Tsuchiya Fengli Guo Xia Zhao Timothy J Corbin MaryEllen Kirkman Kym Delventhal Emma L Moore Sean McKinney Rita Shiang Paul A Trainor rRNA transcription is integral to phase separation and maintenance of nucleolar structure. PLoS Genetics |
| title | rRNA transcription is integral to phase separation and maintenance of nucleolar structure. |
| title_full | rRNA transcription is integral to phase separation and maintenance of nucleolar structure. |
| title_fullStr | rRNA transcription is integral to phase separation and maintenance of nucleolar structure. |
| title_full_unstemmed | rRNA transcription is integral to phase separation and maintenance of nucleolar structure. |
| title_short | rRNA transcription is integral to phase separation and maintenance of nucleolar structure. |
| title_sort | rrna transcription is integral to phase separation and maintenance of nucleolar structure |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010854&type=printable |
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