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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE140622 | GEO | 2020/07/09

REPOSITORIES: GEO

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Project description:ncRNA expression, including snoRNAs, across 11 tissues using polyA-neutral amplification Non-coding RNAs (ncRNAs) are an essential class of molecular species that have been difficult to monitor on high throughput platforms due to frequent lack of polyadenylation. Using a polyadenylation-neutral amplification protocol and next-generation sequencing, we explore ncRNA expression in eleven human tissues. ncRNAs 7SL, U2, 7SK, and HBII-52 are expressed at levels far exceeding mRNAs. C/D and H/ACA box snoRNAs are associated with rRNA methylation and pseudouridylation, respectively: spleen expresses both, hypothalamus expresses mainly C/D box snoRNAs, and testes show enriched expression of both H/ACA box snoRNAs and RNA telomerase TERC. Within the snoRNA 14q cluster, 14q(I-6) is expressed at much higher levels than other cluster members. More reads align to mitochondrial than nuclear tRNAs. Many lincRNAs are actively transcribed, particularly those overlapping known ncRNAs. Within the Prader-Willi syndrome loci, the snoRNA HBII-85 (group I) cluster is highly expressed in hypothalamus, greater than in other tissues and greater than group II or III. Additionally, within the disease locus we find novel transcription across a 400,000 nt span in ovaries. This genome-wide polyA-neutral expression compendium demonstrates the richness of ncRNA expression, their high expression patterns, their function-specific expression patterns, and is publicly available. ArrayExpress Release Date: 2010-07-05 Publication Title: ncRNA expression, including snoRNAs, across 11 tissues using polyA-neutral amplification Publication Author List: Matthew Biery,Heather Bouzek,Ronghua Chen,Stuart Jackson,Jason M. Johnson,Carol A. Rohl,Chris K. Raymond,David Haynor,Christopher D. Armour,John C. Castle Person Roles: submitter Person Last Name: Loewer Person First Name: Martin Person Mid Initials: Person Email: martin.loewer@tron-mainz.de Person Phone: +49 6131-720298-11 Person Address: TRON Translationale Onkologie gGmbH, Langenbeckstr. 8, D-55131 Mainz Person Affiliation: TRON

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

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