m+Medelevator.RU
← Поиск публикаций
medRxiv : the preprint server for health sciences · 2025

De novo and inherited dominant variants in U4 and U6 snRNAs cause retinitis pigmentosa.

СтатьяПрепринтНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…

История · было → стало

Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.

Quinodoz Mathieu, Rodenburg Kim, Cvackova Zuzana, Kaminska Karolina, de Bruijn Suzanne E, Iglesias-Romero Ana Belén, Boonen Erica G M, Ullah Mukhtar, Zomer Nick, Folcher Marc, Bijon Jacques, Holtes Lara K, Tsang Stephen H, Corradi Zelia, Freund K Bailey, Shliaga Stefanida, Panneman Daan M, Hitti-Malin Rebekkah J, Ali Manir, AlTalbishi Ala'a, Andréasson Sten, Ansari Georg, Arno Gavin, Astuti Galuh D N, Ayuso Carmen, Ayyagari Radha, Banfi Sandro, Banin Eyal, Barboni Mirella T S, Bauwens Miriam, Ben-Yosef Tamar, Birch David G, Biswas Pooja, Blanco-Kelly Fiona, Bocquet Beatrice, Boon Camiel J F, Branham Kari, Britten-Jones Alexis Ceecee, Bujakowska Kinga M, Cadena Elizabeth L, Calzetti Giacomo, Cancellieri Francesca, Cattaneo Luca, Issa Peter Charbel, Chadderton Naomi, Coutinho-Santos Luísa, Daiger Stephen P, De Baere Elfride, de la Cerda Berta, De Roach John N, De Zaeytijd Julie, Derks Ronny, Dhaenens Claire-Marie, Dudakova Lubica, Duncan Jacque L, Farrar G Jane, Feltgen Nicolas, Fernández-Caballero Lidia, Sallum Juliana M Ferraz, Gana Simone, Garanto Alejandro, Gardner Jessica C, Gilissen Christian, Goto Kensuke, Gonzàlez-Duarte Roser, Griffiths-Jones Sam, Haack Tobias B, Haer-Wigman Lonneke, Hardcastle Alison J, Hayashi Takaaki, Héon Elise, Hoischen Alexander, Holtan Josephine P, Hoyng Carel B, Ibanez Manuel Benjamin B, Inglehearn Chris F, Iwata Takeshi, Jones Kaylie, Kalatzis Vasiliki, Kamakari Smaragda, Karali Marianthi, Kellner Ulrich, Knézy Krisztina, Klaver Caroline C W, Koenekoop Robert K, Kohl Susanne, Kominami Taro, Kühlewein Laura, Lamey Tina M, Leroy Bart P, Martín-Gutiérrez María Pilar, Martins Nelson, Mauring Laura, Leibu Rina, Lin Siying, Liskova Petra, Lopez Irma, López-Rodríguez Victor R de J, Mahroo Omar A, Manes Gaël, McKibbin Martin, McLaren Terri L, Meunier Isabelle, Michaelides Michel, Millán José M, Mizobuchi Kei, Mukherjee Rajarshi, Nagy Zoltán Zsolt, Neveling Kornelia, Ołdak Monika, Oorsprong Michiel, Pan Yang, Papachristou Anastasia, Percesepe Antonio, Pfau Maximilian, Pierce Eric A, Place Emily, Ramesar Raj, Rasquin Florence Andrée, Rice Gillian I, Roberts Lisa, Rodríguez-Hidalgo María, Ruiz-Eddera Javier, Sabir Ataf H, Sajiki Ai Fujita, Sánchez-Barbero Ana Isabel, Sarma Asodu Sandeep, Sangermano Riccardo, Santos Cristina M, Scarpato Margherita, Scholl Hendrik P N, Sharon Dror, Signorini Sabrina Giovanna, Simonelli Francesca, Sousa Ana Berta, Stefaniotou Maria, Stingl Katarina, Suga Akiko, Sullivan Lori S, Szabó Viktória, Szaflik Jacek P, Taurina Gita, Toomes Carmel, Tran Viet H, Tsilimbaris Miltiadis K, Tsoka Pavlina, Vaclavik Veronika, Vajter Marie, Valeina Sandra, Valente Enza Maria, Valentine Casey, Valero Rebeca, van Aerschot Joseph, van den Born L Ingeborgh, Webster Andrew R, Whelan Laura, Wissinger Bernd, Yioti Georgia G, Yoshitake Kazutoshi, Zenteno Juan C, Zeuli Roberta, Zuleger Theresia, Landau Chaim, Jacob Allan I, Cremers Frans P M, Lee Winston, Ellingford Jamie M, Stanek David, Rivolta Carlo, Roosing Susanne

Аннотация

The U4 small nuclear RNA (snRNA) forms a duplex with the U6 snRNA and, together with U5 and ~30 proteins, is part of the U4/U6.U5 tri-snRNP complex, located at the core of the major spliceosome. Recently, recurrent de novo variants in the U4 RNA, transcribed from the RNU4-2 gene, and in at least two other RNU genes were discovered to cause neurodevelopmental disorder. We detected inherited and de novo heterozygous variants in RNU4-2 (n.18_19insA and n.56T>C) and in four out of the five RNU6 paralogues (n.55_56insG and n.56_57insG) in 135 individuals from 62 families with non-syndromic retinitis pigmentosa (RP), a rare form of hereditary blindness. We show that these variants are recurrent among RP families and invariably cluster in close proximity within the three-way junction (between stem-I, the 5' stem-loop and stem-II) of the U4/U6 duplex, affecting its natural conformation. Interestingly, this region binds to numerous splicing factors of the tri-snRNP complex including PRPF3, PRPF8 and PRPF31, previously associated with RP as well. The U4 and U6 variants identified seem to affect snRNP biogenesis, namely the U4/U6 di-snRNP, which is an assembly intermediate of the tri-snRNP. Based on the number of positive cases observed, deleterious variants in RNU4-2 and in RNU6 paralogues could be a significant cause of isolated or dominant RP, accounting for up to 1.2% of all undiagnosed RP cases. This study highlights the role of non-coding genes in rare Mendelian disorders and uncovers pleiotropy in RNU4-2, where different variants underlie neurodevelopmental disorder and RP.

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты