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Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE140623 | GEO | 2020/07/09

REPOSITORIES: GEO

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Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing [Nano77]

Project description:H/ACA small nucleolar RNAs (snoRNAs) guide pseudouridylation as part of a small nucleolar ribonucleoprotein complex (snoRNP). Disruption of H/ACA snoRNA expression in stem cells impairs pluripotency, yet it remains unclear how H/ACA snoRNAs contribute to differentiation. To determine if H/ACA snoRNA expression is dynamic during differentiation, we comprehensively profiled H/ACA snoRNA expression in multiple murine cell types and during differentiation in three cellular models, including mouse embryonic stem cells and mouse myoblasts. We determined that H/ACA snoRNA expression is cell-type specific, and we identified a subset of snoRNAs that are specifically regulated during differentiation. Additionally, we demonstrated that a decrease in Snora27 expression upon differentiation corresponds to a decrease in pseudouridylation of its target site within the E-site transfer RNA (tRNA) binding region of the 28S ribosomal RNA (rRNA) in the large ribosomal subunit. Many of the snoRNAs regulated during differentiation have target nucleotides in the 28S rRNA, and we found that pre-rRNA processing of large subunit precursors is altered during differentiation. Together, these data suggest a model in which H/ACA snoRNAs are specifically regulated during differentiation to potentially alter pseudouridylation and fine tune ribosome function.

2020-07-09 | GSE140622 | GEO

Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing [Nano104]

2020-07-09 | GSE140618 | GEO

Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing [RNA-seq and ncRNA-seq]

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Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing

Project description:Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing

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Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing [Nano104]

Project description:Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing [Nano104]

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Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing [Nano77]

Project description:Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing [Nano77]

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Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing [RNA-seq and ncRNA-seq]

Project description:Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing [RNA-seq and ncRNA-seq]

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Regulation of translation by ribosomal RNA pseudouridylation.

Project description:Pseudouridine is enriched in ribosomal, spliceosomal, transfer, and messenger RNA and thus integral to the central dogma. The chemical basis for how pseudouridine affects the molecular apparatus such as ribosome, however, remains elusive owing to the lack of structures without this natural modification. Here, we studied the translation of a hypopseudouridylated ribosome initiated by the internal ribosome entry site (IRES) elements. We analyzed eight cryo-electron microscopy structures of the ribosome bound with the Taura syndrome virus IRES in multiple functional states. We found widespread loss of pseudouridine-mediated interactions through water and long-range base pairings. In the presence of the translocase, eukaryotic elongation factor 2, and guanosine 5'-triphosphate hydrolysis, the hypopseudouridylated ribosome favors a rare unconducive conformation for decoding that is partially recouped in the ribosome population that remains modified at the P-site uridine. The structural principles learned establish the link between functional defects and modification loss and are likely applicable to other pseudouridine-associated processes.

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UtpA and UtpB chaperone nascent pre-ribosomal RNA and U3 snoRNA to initiate eukaryotic ribosome assembly.

Project description:Early eukaryotic ribosome biogenesis involves large multi-protein complexes, which co-transcriptionally associate with pre-ribosomal RNA to form the small subunit processome. The precise mechanisms by which two of the largest multi-protein complexes-UtpA and UtpB-interact with nascent pre-ribosomal RNA are poorly understood. Here, we combined biochemical and structural biology approaches with ensembles of RNA-protein cross-linking data to elucidate the essential functions of both complexes. We show that UtpA contains a large composite RNA-binding site and captures the 5' end of pre-ribosomal RNA. UtpB forms an extended structure that binds early pre-ribosomal intermediates in close proximity to architectural sites such as an RNA duplex formed by the 5' ETS and U3 snoRNA as well as the 3' boundary of the 18S rRNA. Both complexes therefore act as vital RNA chaperones to initiate eukaryotic ribosome assembly.

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