title: pY RNA1-s2: a highly retina-enriched small RNA that selectively binds to Matrin 3 (Matr3).
abstract: The purpose of this study was to expand our knowledge of small RNAs, which are known to function within protein complexes to modulate the transcriptional output of the cell. Here we describe two previously unrecognized, small RNAs, termed pY RNA1-s1 and pY RNA1-s2 (processed Y RNA1-stem -1 and -2), thereby expanding the list of known small RNAs. pY RNA1-s1 and pY RNA1-s2 were discovered by RNA sequencing and found to be 20-fold more abundant in the retina than in 14 other rat tissues. Retinal expression of pY RNAs is highly conserved, including expression in the human retina, and occurs in all retinal cell layers. Mass spectrometric analysis of pY RNA1-S2 binding proteins in retina indicates that pY RNA1-s2 selectively binds the nuclear matrix protein Matrin 3 (Matr3) and to a lesser degree to hnrpul1 (heterogeneous nuclear ribonucleoprotein U-like protein). In contrast, pY RNA1-s1 does not bind these proteins. Accordingly, the molecular mechanism of action of pY RNA1-s2 is likely be through an action involving Matr3; this 95 kDa protein has two RNA recognition motifs (RRMs) and is implicated in transcription and RNA-editing. The high affinity binding of pY RNA1-s2 to Matr3 is strongly dependent on the sequence of the RNA and both RRMs of Matr3. Related studies also indicate that elements outside of the RRM region contribute to binding specificity and that phosphorylation enhances pY RNA-s2/Matr3 binding. These observations are of significance because they reveal that a previously unrecognized small RNA, pY RNA1-s2, binds selectively to Matr3. Hypothetically, pY RNA1-S2 might act to modulate cellular function through this molecular mechanism. The retinal enrichment of pY RNA1-s2 provides reason to suspect that the pY RNA1-s2/Matr3 interaction could play a role in vision.
authors.affiliation: Section on Neuroendocrinology, Program in Developmental Endocrinology and Genetics, The Eunice Shriver Kennedy National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Yamazaki
authors.affiliation: Section on Neuroendocrinology, Program in Developmental Endocrinology and Genetics, The Eunice Shriver Kennedy National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Hyun Hee
authors.initials: HH
authors.lastname: Kim
authors.affiliation: Division of intramural research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lau
authors.affiliation: Departments of Ophthalmology and Pharmacology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Hwang
authors.affiliation: Departments of Ophthalmology and Pharmacology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: P Michael
authors.initials: PM
authors.lastname: Iuvone
authors.affiliation: Section on Neuroendocrinology, Program in Developmental Endocrinology and Genetics, The Eunice Shriver Kennedy National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Klein
authors.affiliation: Section on Neuroendocrinology, Program in Developmental Endocrinology and Genetics, The Eunice Shriver Kennedy National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Samuel J H
authors.initials: SJ
authors.lastname: Clokie
mesh_terms: D000328:Adult; D020816:Amino Acid Motifs; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002645:Chickens; D005260:Female; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D013058:Mass Spectrometry; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D008969:Molecular Sequence Data; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D010766:Phosphorylation; D010870:Pineal Gland / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D058727:RNA, Small Untranslated / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism*; D012756:Sheep; D014018:Tissue Distribution
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; C518587:MATR3 protein, human; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D058727:RNA, Small Untranslated; D016601:RNA-Binding Proteins; C573692:matrin-3 protein, mouse; C068873:matrin 3, rat