Pseudouridylation defect due to
            <i>DKC1</i>
            and
            <i>NOP10</i>
            mutations causes nephrotic syndrome with cataracts, hearing impairment, and enterocolitis

Balogh, Eszter; Chandler, Jennifer C.; Varga, Máté; Tahoun, Mona; Menyhárd, Dóra K.; Schay, Gusztáv; Goncalves, Tomas; Hamar, Renáta; Légrádi, Regina; Szekeres, Ákos; Gribouval, Olivier; Kleta, Robert; Stanescu, Horia; Böckenhauer, Detlef; Kerti, Andrea; Hj, Williams; Kinsler, Veronica A.; Di, Wei‐Li; Curtis, David; Kolatsi-Joannou, Maria; Hammid, Hafsa; Szőcs, Anna; Perczel, Kristóf; Maka, Erika; Toldi, Gergely; Sava, Florentina; Arrondel, Christelle; Kardos, Magdolna; Fintha, Attila; Hossain, Ahmed; D'arco, Felipe; Kaliakatsos, Mario; Köeglmeier, Jutta; Mifsud, William; Moosajee, Mariya; Faro, Ana; Jávorszky, Eszter; Rudas, Gábor; Saied, Marwa H.; Marzouk, Salah; Kelen, Kata; Götze, Judit; Reusz, George; Tulassay, Tivadar; Dragon, François; Mollet, Géraldine; Motameny, Susanne; Thiele, Holger; Dorval, Guillaume; Nürnberg, Peter; Perczel, András; Szabó, Attila; Long, David A.; Tomita, Kazunori; Antignac, Corinne; Waters, Aoife; Tory, Kálmán

doi:10.1073/pnas.2002328117

Cited by 34 publications

(27 citation statements)

References 78 publications

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“…As with TERC itself, mutations in DKC1 , NOP10 , NHP2 , and NAF1 have not been found in null states, which are unlikely to be tolerated. It remains unclear whether other sno/scaRNAs or pseudouridylation are meaningfully impacted by these mutations, with evidence for and against relevant effects in various studies 29,75‐82 . However, it is clear that TERC is affected by these mutations.…”

Section: Mutations In Several Factors Impact Terc To Cause Diseasementioning

confidence: 99%

Telomerase RNA processing: Implications for human health and disease

Nagpal

Agarwal

2020

Stem Cells

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Telomeres are composed of repetitive DNA sequences that are replenished by the enzyme telomerase to maintain the self-renewal capacity of stem cells. The RNA component of human telomerase (TERC) is the essential template for repeat addition by the telomerase reverse transcriptase (TERT), and also serves as a scaffold for several factors comprising the telomerase ribonucleoprotein (RNP). Unique features of TERC regulation and function have been informed not only through biochemical studies but also through human genetics. Disease-causing mutations impact TERC biogenesis at several levels including RNA transcription, posttranscriptional processing, folding, RNP assembly, and trafficking. Defects in TERC reduce telomerase activity and impair telomere maintenance, thereby causing a spectrum of degenerative diseases called telomere biology disorders (TBDs). Deciphering mechanisms of TERC dysregulation have led to a broader understanding of noncoding RNA biology, and more recently points to new therapeutic strategies for TBDs. In this review, we summarize over two decades of work revealing mechanisms of human telomerase RNA biogenesis, and how its disruption causes human diseases.

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Section: Mutations In Several Factors Impact Terc To Cause Diseasementioning

confidence: 99%

Telomerase RNA processing: Implications for human health and disease

Nagpal

Agarwal

2020

Stem Cells

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“…The writers for Ψ are pseudouridine synthases (PUSs), which can be RNA dependent or RNA-independent. An additional adjuvant writer is dyskerin pseudouridine synthase 1 (DKC1) which mainly targets ncRNAs [ 145 ]. Up-regulation of DKC1 is associated with worse prognosis in lung and pancreatic cancer [ 146 , 147 ].…”

Section: Ncrna Chemical Modifications In Cancermentioning

confidence: 99%

Editing and Chemical Modifications on Non-Coding RNAs in Cancer: A New Tale with Clinical Significance

Torsin

Petrescu

Sabo

et al. 2021

IJMS

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Currently, for seemingly every type of cancer, dysregulated levels of non-coding RNAs (ncRNAs) are reported and non-coding transcripts are expected to be the next class of diagnostic and therapeutic tools in oncology. Recently, alterations to the ncRNAs transcriptome have emerged as a novel hallmark of cancer. Historically, ncRNAs were characterized mainly as regulators and little attention was paid to the mechanisms that regulate them. The role of modifications, which can control the function of ncRNAs post-transcriptionally, only recently began to emerge. Typically, these modifications can be divided into reversible (i.e., chemical modifications: m5C, hm5C, m6A, m1A, and pseudouridine) and non-reversible (i.e., editing: ADAR dependent, APOBEC dependent and ADAR/APOBEC independent). The first research papers showed that levels of these modifications are altered in cancer and can be part of the tumorigenic process. Hence, the aim of this review paper is to describe the most common regulatory modifications (editing and chemical modifications) of the traditionally considered “non-functional” ncRNAs (i.e., microRNAs, long non-coding RNAs and circular RNAs) in the context of malignant disease. We consider that only by understanding this extra regulatory layer it is possible to translate the knowledge about ncRNAs and their modifications into clinical practice.

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“…Together with other factors, the PUS10 gene was identified as a risk locus in Crohn's disease, an inflammatory disease [31]. Recently, clinical-relevant mutations in DKC1 and NOP10 have been proven to reduce pseudouridylation in rRNAs and cause nephrotic syndromes in fish [24]. In addition, aberrant pseudouridylation profiles have been linked to cancer formation [32].…”

Section: Hspus1mentioning

confidence: 99%