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

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Quinodoz M
  • Rodenburg K
  • Cvackova Z
  • Kaminska K
  • de Bruijn SE
  • Iglesias-Romero AB
  • Boonen EGM
  • Ullah M
  • Zomer N
  • Folcher M
  • Bijon J
  • Holtes LK
  • Tsang SH
  • Corradi Z
  • Freund KB
  • Shliaga S
  • Panneman DM
  • Hitti-Malin RJ
  • Ali M
  • AlTalbishi A
  • Andréasson S
  • Ansari G
  • Arno G
  • Astuti GDN
  • Ayuso C
  • Ayyagari R
  • Banfi S
  • Banin E
  • Barakat TS
  • Barboni MTS
  • Bauwens M
  • Ben-Yosef T
  • Bernard V
  • Birch DG
  • Biswas P
  • Blanco-Kelly F
  • Bocquet B
  • Boon CJF
  • Branham K
  • Bremond-Gignac D
  • Britten-Jones AC
  • Bujakowska KM
  • Burin des Roziers C
  • Cadena EL
  • Calzetti G
  • Cancellieri F
  • Cattaneo L
  • Chadderton N
  • Charbel Issa P
  • Coutinho-Santos L
  • Daiger SP
  • De Baere E
  • De Bruyne M
  • de la Cerda B
  • De Roach JN
  • De Zaeytijd J
  • Derks R
  • Dhaenens CM
  • Dudakova L
  • Duncan JL
  • Farrar GJ
  • Feltgen N
  • Fenner BJ
  • Fernández-Caballero L
  • Ferraz Sallum JM
  • Gana S
  • Garanto A
  • Gardner JC
  • Gilissen C
  • Gonzàlez-Duarte R
  • Goto K
  • Griffiths-Jones S
  • Haack TB
  • Haer-Wigman L
  • Hardcastle AJ
  • Hayashi T
  • Héon E
  • Hoefsloot LH
  • Hoischen A
  • Holtan JP
  • Hoyng CB
  • Ibanez MBB 4th
  • Inglehearn CF
  • Iwata T
  • Jensson BO
  • Jones K
  • Kalatzis V
  • Kamakari S
  • Karali M
  • Kellner U
  • Klaver CCW
  • Knézy K
  • Koenekoop RK
  • Kohl S
  • Kominami T
  • Kühlewein L
  • Lamey TM
  • Leibu R
  • Leroy BP
  • Liskova P
  • Lopez I
  • López-Rodríguez VRJ
  • Mahieu Q
  • Mahroo OA
  • Manes G
  • Mansard L
  • Martín-Gutiérrez MP
  • Martins N
  • Mauring L
  • McKibbin M
  • McLaren TL
  • Meunier I
  • Michaelides M
  • Mizobuchi K
  • Mukherjee R
  • Nagy ZZ
  • Neveling K
  • Oldak M
  • Oorsprong M
  • Pan Y
  • Papachristou A
  • Percesepe A
  • Pfau M
  • Pierce EA
  • Place E
  • Ramesar R
  • Ramond F
  • Rasquin FA
  • Rice GI
  • Roberts L
  • Rodríguez-Hidalgo M
  • Ruiz-Ederra J
  • Sabir AH
  • Sajiki AF
  • Sánchez-Barbero AI
  • Sarma AS
  • Sangermano R
  • Santos CM
  • Scarpato M
  • Scholl HPN
  • Sharon D
  • Signorini SG
  • Simonelli F
  • Sousa AB
  • Stefaniotou M
  • Stefansson K
  • Stingl K
  • Suga A
  • Sulem P
  • Sullivan LS
  • Szabó V
  • Szaflik JP
  • Taurina G
  • Thiadens AAHJ
  • Toomes C
  • Tran VH
  • Tsilimbaris MK
  • Tsoka P
  • Vaclavik V
  • Vajter M
  • Valeina S
  • Valente EM
  • Valentine C
  • Valero R
  • Valleix S
  • van Aerschot J
  • van den Born LI
  • Van Heetvelde M
  • Verhoeven VJM
  • Vincent AL
  • Webster AR
  • Whelan L
  • Wissinger B
  • Yioti GG
  • Yoshitake K
  • Zenteno JC
  • Zeuli R
  • Zuleger T
  • Landau C
  • Jacob AI
  • Lin S
  • Cremers FPM
  • Lee W
  • Ellingford JM
  • Stanek D
  • Roosing S
  • Rivolta C

Grupos

Abstract

Small nuclear RNAs (snRNAs) combine with specific proteins to generate small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. U4 snRNA forms a duplex with U6 and, together with U5, contributes to the tri-snRNP spliceosomal complex. Variants in RNU4-2, which encodes U4, have recently been implicated in neurodevelopmental disorders. Here we show that heterozygous inherited and de novo variants in RNU4-2 and in four RNU6 paralogs (RNU6-1, RNU6-2, RNU6-8 and RNU6-9), which encode U6, recur in individuals with nonsyndromic retinitis pigmentosa (RP), a genetic disorder causing progressive blindness. These variants cluster within the three-way junction of the U4/U6 duplex, a site that interacts with tri-snRNP splicing factors also known to cause RP (PRPF3, PRPF8, PRPF31), and seem to affect snRNP biogenesis. Based on our cohort, deleterious variants in RNU4-2 and RNU6 paralogs may explain up to ~1.4% of otherwise undiagnosed RP cases. This study highlights the contribution of noncoding RNA genes to Mendelian disease and reveals pleiotropy in RNU4-2, where distinct variants underlie neurodevelopmental disorder and retinal degeneration.

© 2026. The Author(s).

Datos de la publicación

ISSN/ISSNe:
1061-4036, 1546-1718

NATURE GENETICS  NATURE PORTFOLIO

Tipo:
Article
Páginas:
169-179
PubMed:
41513982
Enlace a otro recurso:
www.scopus.com
Factor de Impacto:
16,517 SCImago
Cuartil:
Q1 SCImago

Citas Recibidas en Web of Science: 7

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Keywords

  • small nuclear ribonucleoprotein; small nuclear RNA; transcriptome; untranslated RNA; U4 small nuclear RNA; U6 small nuclear RNA; adult; Article; biogenesis; cohort analysis; controlled study; genetic variation; human; major clinical study; mental disease; middle aged; monogenic disorder; paralogy; pleiotropy; protein secondary structure; retina degeneration; retinitis pigmentosa; RNA splicing; Sanger sequencing; dominant gene; female; genetics; male; mutation; pedigree; spliceosome; Female; Genes, Dominant; Humans; Male; Mutation; Pedigree; Retinitis Pigmentosa; Ribonucleoprotein, U4-U6 Small Nuclear; Ribonucleoproteins, Small Nuclear; RNA, Small Nuclear; Spliceosomes

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