| Literature DB >> 30526862 |
Arjan P M de Brouwer1, Rami Abou Jamra2, Nadine Körtel3, Clara Soyris4, Daniel L Polla5, Modi Safra4, Avia Zisso4, Christopher A Powell6, Pedro Rebelo-Guiomar6, Nadja Dinges3, Violeta Morin3, Michael Stock3, Mureed Hussain7, Mohsin Shahzad8, Saima Riazuddin9, Zubair M Ahmed9, Rolph Pfundt10, Franziska Schwarz10, Lonneke de Boer11, André Reis12, Detilina Grozeva13, F Lucy Raymond13, Sheikh Riazuddin14, David A Koolen10, Michal Minczuk6, Jean-Yves Roignant3, Hans van Bokhoven10, Schraga Schwartz15.
Abstract
We describe six persons from three families with three homozygous protein truncating variants in PUS7: c.89_90del (p.Thr30Lysfs∗20), c.1348C>T (p.Arg450∗), and a deletion of the penultimate exon 15. All these individuals have intellectual disability with speech delay, short stature, microcephaly, and aggressive behavior. PUS7 encodes the RNA-independent pseudouridylate synthase 7. Pseudouridylation is the most abundant post-transcriptional modification in RNA, which is primarily thought to stabilize secondary structures of RNA. We show that the disease-related variants lead to abolishment of PUS7 activity on both tRNA and mRNA substrates. Moreover, pus7 knockout in Drosophila melanogaster results in a number of behavioral defects, including increased activity, disorientation, and aggressiveness supporting that neurological defects are caused by PUS7 variants. Our findings demonstrate that RNA pseudouridylation by PUS7 is essential for proper neuronal development and function.Entities:
Keywords: Drosophila melanogaster; aggressive behavior; growth delay; intellectual disability; mRNA substrates; microcephaly; neurodevelopmental delay; pseudouridylation; speech delay; tRNA
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Year: 2018 PMID： 30526862 PMCID： PMC6288278 DOI： 10.1016/j.ajhg.2018.10.026
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025