title: Sjogren syndrome antigen B (SSB)/La promotes global microRNA expression by binding microRNA precursors through stem-loop recognition.
abstract: MicroRNAs (miRNA) control numerous physiological and pathological processes. Typically, the primary miRNA (pri-miRNA) transcripts are processed by nuclear Drosha complex into ~70-nucleotide stem-loop precursor miRNAs (pre-miRNA), which are further cleaved by cytoplasmic Dicer complex into ~21-nucleotide mature miRNAs. However, it is unclear how nascent pre-miRNAs are protected from ribonucleases, such as MCPIP1, that degrade pre-miRNAs to abort miRNA production. Here, we identify Sjögren syndrome antigen B (SSB)/La as a pre-miRNA-binding protein that regulates miRNA processing in vitro. All three RNA-binding motifs (LAM, RRM1, and RRM2) of La/SSB are required for efficient pre-miRNA binding. Intriguingly, La/SSB recognizes the characteristic stem-loop structure of pre-miRNAs, of which the majority lack a 3' UUU terminus. Moreover, La/SSB associates with endogenous pri-/pre-miRNAs and promotes miRNA biogenesis by stabilizing pre-miRNAs from nuclease (e.g. MCPIP1)-mediated decay in mammalian cells. Accordingly, we observed positive correlations between the expression status of La/SSB and Dicer in human cancer transcriptome and prognosis. These studies identify an important function of La/SSB as a global regulator of miRNA expression, and implicate stem-loop recognition as a major mechanism that mediates association between La/SSB and diverse RNA molecules.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Liang
authors.forename: Ke
authors.initials: K
authors.lastname: Xiong
authors.forename: Keith E
authors.initials: KE
authors.lastname: Szulwach
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Wang
authors.forename: Junmin
authors.initials: J
authors.lastname: Peng
authors.forename: Mingui
authors.initials: M
authors.lastname: Fu
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.forename: Hiroshi I
authors.initials: HI
authors.lastname: Suzuki
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Liu
mesh_terms: D001324:Autoantigens / Q000378:metabolism*; D015551:Autoimmunity; D003593:Cytoplasm / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D035683:MicroRNAs / Q000378:metabolism*; D008954:Models, Biological; D017433:Protein Structure, Secondary; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000378:metabolism*; D000097585:SS-B Antigen
chemical_list: D001324:Autoantigens; D053487:DEAD-box RNA Helicases; D035683:MicroRNAs; D012313:RNA; D016601:RNA-Binding Proteins; D043244:Ribonuclease III; D012260:Ribonucleases; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; C408087:DICER1 protein, human