@article {351,
	title = {Biallelic mutations in the 3{\textquoteright} exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing.},
	journal = {Nat Genet},
	volume = {49},
	year = {2017},
	month = {2017 Mar},
	pages = {457-464},
	abstract = {<p>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{\textquoteright}-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{\textquoteright} genome-encoded tails often followed by post-transcriptionally added adenosines. Human cells with reduced levels of TOE1 accumulated 3{\textquoteright}-end-extended pre-snRNAs, and the immunoisolated TOE1 complex was sufficient for 3{\textquoteright}-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{\textquoteright} ends.</p>},
	keywords = {Alleles, Animals, Cerebellar Diseases, Exonucleases, Female, Humans, Male, Mice, Mutation, Neurodegenerative Diseases, Nuclear Proteins, RNA, Messenger, RNA, Small Nuclear, Spliceosomes, Zebrafish},
	issn = {1546-1718},
	doi = {10.1038/ng.3762},
	author = {Lardelli, Rea M and Schaffer, Ashleigh E and Eggens, Veerle R C and Zaki, Maha S and Grainger, Stephanie and Sathe, Shashank and Van Nostrand, Eric L and Schlachetzki, Zinayida and Rosti, Basak and Akizu, Naiara and Scott, Eric and Silhavy, Jennifer L and Heckman, Laura Dean and Rosti, Rasim Ozgur and Dikoglu, Esra and Gregor, Anne and Guemez-Gamboa, Alicia and Musaev, Damir and Mande, Rohit and Widjaja, Ari and Shaw, Tim L and Markmiller, Sebastian and Marin-Valencia, Isaac and Davies, Justin H and de Meirleir, Linda and Kayserili, H{\"u}lya and Altunoglu, Umut and Freckmann, Mary Louise and Warwick, Linda and Chitayat, David and Blaser, Susan and {\c C}a{\u g}layan, Ahmet Okay and Bilguvar, Kaya and Per, H{\"u}seyin and Fagerberg, Christina and Christesen, Henrik T and Kibaek, Maria and Aldinger, Kimberly A and Manchester, David and Matsumoto, Naomichi and Muramatsu, Kazuhiro and Saitsu, Hirotomo and Shiina, Masaaki and Ogata, Kazuhiro and Foulds, Nicola and Dobyns, William B and Chi, Neil C and Traver, David and Spaccini, Luigina and Bova, Stefania Maria and Gabriel, Stacey B and G{\"u}nel, Murat and Valente, Enza Maria and Nassogne, Marie-Cecile and Bennett, Eric J and Yeo, Gene W and Baas, Frank and Lykke-Andersen, Jens and Gleeson, Joseph G}
}
@article {252,
	title = {CLP1 founder mutation links tRNA splicing and maturation to cerebellar development and neurodegeneration.},
	journal = {Cell},
	volume = {157},
	year = {2014},
	month = {2014 Apr 24},
	pages = {651-63},
	abstract = {<p>Neurodegenerative diseases can occur so early as to affect neurodevelopment. From a cohort of more than 2,000 consanguineous families with childhood neurological disease, we identified a founder mutation in four independent pedigrees in cleavage and polyadenylation factor I subunit 1 (CLP1). CLP1 is a multifunctional kinase implicated in tRNA, mRNA, and siRNA maturation. Kinase activity of the CLP1 mutant protein was defective, and the tRNA endonuclease complex (TSEN) was destabilized, resulting in impaired pre-tRNA cleavage. Germline clp1 null zebrafish showed cerebellar neurodegeneration that was rescued by wild-type, but not mutant, human CLP1 expression. Patient-derived induced neurons displayed both depletion of mature tRNAs and accumulation of unspliced pre-tRNAs. Transfection of partially processed tRNA fragments into patient cells exacerbated an oxidative stress-induced reduction in cell survival. Our data link tRNA maturation to neuronal development and neurodegeneration through defective CLP1 function in humans.</p>},
	keywords = {Animals, Brain, Cerebellum, Cleavage And Polyadenylation Specificity Factor, Female, Humans, Male, Mice, Models, Molecular, Neurodegenerative Diseases, Nuclear Proteins, Pedigree, Phosphotransferases, RNA Splicing, RNA, Transfer, Saccharomyces cerevisiae, Transcription Factors, Zebrafish, Zebrafish Proteins},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2014.03.049},
	author = {Schaffer, Ashleigh E and Eggens, Veerle R C and {\c C}a{\u g}layan, Ahmet Okay and Reuter, Miriam S and Scott, Eric and Coufal, Nicole G and Silhavy, Jennifer L and Xue, Yuanchao and Kayserili, H{\"u}lya and Yasuno, Katsuhito and Rosti, Rasim Ozgur and Abdellateef, Mostafa and Caglar, Caner and Kasher, Paul R and Cazemier, J Leonie and Weterman, Marian A and Cantagrel, Vincent and Cai, Na and Zweier, Christiane and Altunoglu, Umut and Satkin, N Bilge and Aktar, Fesih and Tuysuz, Beyhan and Yalcinkaya, Cengiz and Caksen, Huseyin and Bilguvar, Kaya and Fu, Xiang-Dong and Trotta, Christopher R and Gabriel, Stacey and Reis, Andr{\'e} and G{\"u}nel, Murat and Baas, Frank and Gleeson, Joseph G}
}
