Details

Autor(en) / Beteiligte

• Lardelli, Rea M
• Schaffer, Ashleigh E
• Eggens, Veerle R C
• Zaki, Maha S
• Grainger, Stephanie
• Sathe, Shashank
• Van Nostrand, Eric L
• Schlachetzki, Zinayida
• Rosti, Basak
• Akizu, Naiara
• Scott, Eric
• Silhavy, Jennifer L
• Heckman, Laura Dean
• Rosti, Rasim Ozgur
• Dikoglu, Esra
• Gregor, Anne
• Guemez-Gamboa, Alicia
• Musaev, Damir
• Mande, Rohit
• Widjaja, Ari
• Shaw, Tim L
• Markmiller, Sebastian
• Marin-Valencia, Isaac
• Davies, Justin H
• de Meirleir, Linda
• Kayserili, Hulya
• Altunoglu, Umut
• Freckmann, Mary Louise
• Warwick, Linda
• Chitayat, David
• Blaser, Susan
• Çağlayan, Ahmet Okay
• Bilguvar, Kaya
• Per, Huseyin
• Fagerberg, Christina
• Christesen, Henrik T
• Kibaek, Maria
• Aldinger, Kimberly A
• Manchester, David
• Matsumoto, Naomichi
• Muramatsu, Kazuhiro
• Saitsu, Hirotomo
• Shiina, Masaaki
• Ogata, Kazuhiro
• Foulds, Nicola
• Dobyns, William B
• Chi, Neil C
• Traver, David
• Spaccini, Luigina
• Bova, Stefania Maria
• Gabriel, Stacey B
• Gunel, Murat
• Valente, Enza Maria
• Nassogne, Marie-Cecile
• Bennett, Eric J
• Yeo, Gene W
• Baas, Frank
• Lykke-Andersen, Jens
• Gleeson, Joseph G

Titel

Biallelic mutations in the 3' exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing

Ist Teil von

• Nature genetics, 2017-03, Vol.49 (3), p.457-464

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Deadenylases are best known for degrading the poly(A) tail during mRNA decay. The deadenylase family has expanded throughout evolution and, in mammals, consists of 12 Mg -dependent 3'-end RNases with substrate specificity that is mostly unknown. Pontocerebellar hypoplasia type 7 (PCH7) is a unique recessive syndrome characterized by neurodegeneration and ambiguous genitalia. We studied 12 human families with PCH7, uncovering biallelic, loss-of-function mutations in TOE1, which encodes an unconventional deadenylase. toe1-morphant zebrafish displayed midbrain and hindbrain degeneration, modeling PCH-like structural defects in vivo. Surprisingly, we found that TOE1 associated with small nuclear RNAs (snRNAs) incompletely processed spliceosomal. These pre-snRNAs contained 3' genome-encoded tails often followed by post-transcriptionally added adenosines. Human cells with reduced levels of TOE1 accumulated 3'-end-extended pre-snRNAs, and the immunoisolated TOE1 complex was sufficient for 3'-end maturation of snRNAs. Our findings identify the cause of a neurodegenerative syndrome linked to snRNA maturation and uncover a key factor involved in the processing of snRNA 3' ends.