title: A thymus-specific noncoding RNA, Thy-ncR1, is a cytoplasmic riboregulator of MFAP4 mRNA in immature T-cell lines.
abstract: BACKGROUND
  Postgenomic transcriptome analyses have identified large numbers of noncoding (nc)RNAs in mammalian cells. However, the biological function of long ncRNAs in mammalian cells remains largely unknown. Our recent expression profiling of selected human long ncRNAs revealed that a majority were expressed in an organ-specific manner, suggesting their function was linked to specific physiological phenomena in each organ. We investigated the characteristics and function of ncRNAs that were specifically expressed in the thymus, the site of T-cell selection and maturation.
  
  
  RESULTS
  Expression profiling of 10 thymus-specific ncRNAs in 17 T-cell leukemia cell lines derived from various stages of T-cell maturation revealed that HIT14168 ncRNA, named Thy-ncR1, was specifically expressed in cell lines derived from stage III immature T cells in which the neighbouring CD1 gene cluster is also specifically activated. The Thy-ncR1 precursor exhibited complex alternative splicing patterns and differential usage of the 5' terminus leading to the production of an estimated 24 isoforms, which were predominantly located in the cytoplasm. Selective RNAi knockdown of each Thy-ncR1 isoform demonstrated that microfibril-associated glycoprotein 4 (MFAP4) mRNA was negatively regulated by two major Thy-ncR1 isoforms. Intriguingly, the MFAP4 mRNA level was controlled by a hUPF1-dependent mRNA degradation pathway in the cytoplasm distinct from nonsense-mediated decay.
  
  
  CONCLUSIONS
  This study identified Thy-ncR1 ncRNA to be specifically expressed in stage III immature T cells in which the neighbouring CD1 gene cluster was activated. Complex alternative splicing produces multiple Thy-ncR1 isoforms. Two major Thy-ncR1 isoforms are cytoplasmic riboregulators that suppress the expression of MFAP4 mRNA, which is degraded by an uncharacterized hUPF1-dependent pathway.
authors.affiliation: Biomedicinal Information Research Center, National Institute of Advanced Industrial Science and Technology, Koutou, Tokyo, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Aoki
authors.forename: Akira
authors.initials: A
authors.lastname: Harashima
authors.forename: Miho
authors.initials: M
authors.lastname: Sano
authors.forename: Takahide
authors.initials: T
authors.lastname: Yokoi
authors.forename: Shuji
authors.initials: S
authors.lastname: Nakamura
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kibata
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Hirose
mesh_terms: D017398:Alternative Splicing; D018949:Antigens, CD1 / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D054504:Precursor Cells, T-Lymphoid / Q000276:immunology / Q000378:metabolism*; D020365:RNA Helicases; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D018949:Antigens, CD1; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C400752:MFAP4 protein, human; D012333:RNA, Messenger; D022661:RNA, Untranslated; D015534:Trans-Activators; D020365:RNA Helicases; C101828:UPF1 protein, human