title: Minor splicing snRNAs are enriched in the developing mouse CNS and are crucial for survival of differentiating retinal neurons.
abstract: In eukaryotes, gene expression requires splicing, which starts with the identification of exon-intron boundaries by the small, nuclear RNA (snRNAs) of the spliceosome, aided by associated proteins. In the mammalian genome, <1% of introns lack canonical exon-intron boundary sequences and cannot be spliced by the canonical splicing machinery. These introns are spliced by the minor spliceosome, consisting of unique snRNAs (U11, U12, U4atac, and U6atac). The importance of the minor spliceosome is underscored by the disease microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1), which is caused by mutation in U4atac. Thus, it is important to understand the expression and function of the minor spliceosome and its targets in mammalian development, for which we used the mouse as our model. Here, we report enrichment of the minor snRNAs in the developing head/central nervous system (CNS) between E9.5 and E12.5, along with enrichment of these snRNAs in differentiating retinal neurons. Moreover, dynamic expression kinetics of minor intron-containing genes (MIGs) was observed across retinal development. DAVID analysis of MIGs that were cotranscriptionally upregulated embryonically revealed enrichment for RNA metabolism and cell cycle regulation. In contrast, MIGs that were cotranscriptionally upregulated postnatally revealed enrichment for protein localization/transport, vesicle-mediated transport, and calcium transport. Finally, we used U12 morpholino to inactivate the minor spliceosome in the postnatal retina, which resulted in apoptosis of differentiating retinal neurons. Taken together, our data suggest that the minor spliceosome may have distinct functions in embryonic versus postnatal development. Importantly, we show that the minor spliceosome is crucial for the survival of terminally differentiating retinal neurons.
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, 06269.
authors.forename: Marybeth
authors.initials: M
authors.lastname: Baumgartner
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, 06269.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lemoine
authors.affiliation: Department of Computer Science and Engineering, University of Connecticut, Storrs, Connecticut, 06269.
authors.forename: Sahar
authors.initials: S
authors.lastname: Al Seesi
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, 06269.
authors.forename: Devi Krishna Priya
authors.initials: DK
authors.lastname: Karunakaran
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, 06269.
authors.forename: Nikita
authors.initials: N
authors.lastname: Sturrock
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, 06269.
authors.forename: Abdul Rouf
authors.initials: AR
authors.lastname: Banday
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, 06269.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Kilcollins
authors.affiliation: Department of Computer Science and Engineering, University of Connecticut, Storrs, Connecticut, 06269.
authors.forename: Ion
authors.initials: I
authors.lastname: Mandoiu
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, 06269.
authors.forename: Rahul N
authors.initials: RN
authors.lastname: Kanadia
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D018274:Electroporation; D006801:Humans; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051379:Mice; D046228:Microarray Analysis; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D060172:Morpholinos; D055495:Neurogenesis; D012342:RNA, Small Nuclear / Q000378:metabolism*; D012160:Retina / Q000196:embryology* / Q000378:metabolism*; D055351:Retinal Neurons / Q000473:pathology / Q000502:physiology*; D017381:Spliceosomes / Q000378:metabolism*
chemical_list: D060172:Morpholinos; D012342:RNA, Small Nuclear
keywords: mammalian development; minor intron-containing genes; minor splicing; neuronal differentiation; retina