3′ End Processing of a Long Nuclear-Retained Noncoding RNA Yields a tRNA-like Cytoplasmic RNA

被引:613
作者
Wilusz, Jeremy E. [1 ]
Freier, Susan M. [2 ]
Spector, David L. [1 ]
机构
[1] Cold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA
[2] ISIS Pharmaceut, Carlsbad, CA 92008 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1016/j.cell.2008.10.012
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
MALAT1 is a long noncoding RNA known to be misregulated in many human cancers. We have identified a highly conserved small RNA of 61 nucleotides originating from the MALAT1 locus that is broadly expressed in human tissues. Although the long MALAT1 transcript localizes to nuclear speckles, the small RNA is found exclusively in the cytoplasm. RNase P cleaves the nascent MALAT1 transcript downstream of a genomically encoded poly(A)-rich tract to simultaneously generate the 30 end of the mature MALAT1 transcript and the 50 end of the small RNA. Enzymes involved in tRNA biogenesis then further process the small RNA, consistent with its adoption of a tRNA-like structure. Our findings reveal a 30 end processing mechanism by which a single gene locus can yield both a stable nuclear-retained noncoding RNA with a short poly(A) tail-like moiety and a small tRNA-like cytoplasmic RNA.
引用
收藏
页码:919 / 932
页数:14
相关论文
共 53 条
  • [1] RNA editing by adenosine deaminases that act on RNA
    Bass, BL
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 2002, 71 : 817 - 846
  • [2] Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
    Birney, Ewan
    Stamatoyannopoulos, John A.
    Dutta, Anindya
    Guigo, Roderic
    Gingeras, Thomas R.
    Margulies, Elliott H.
    Weng, Zhiping
    Snyder, Michael
    Dermitzakis, Emmanouil T.
    Stamatoyannopoulos, John A.
    Thurman, Robert E.
    Kuehn, Michael S.
    Taylor, Christopher M.
    Neph, Shane
    Koch, Christoph M.
    Asthana, Saurabh
    Malhotra, Ankit
    Adzhubei, Ivan
    Greenbaum, Jason A.
    Andrews, Robert M.
    Flicek, Paul
    Boyle, Patrick J.
    Cao, Hua
    Carter, Nigel P.
    Clelland, Gayle K.
    Davis, Sean
    Day, Nathan
    Dhami, Pawandeep
    Dillon, Shane C.
    Dorschner, Michael O.
    Fiegler, Heike
    Giresi, Paul G.
    Goldy, Jeff
    Hawrylycz, Michael
    Haydock, Andrew
    Humbert, Richard
    James, Keith D.
    Johnson, Brett E.
    Johnson, Ericka M.
    Frum, Tristan T.
    Rosenzweig, Elizabeth R.
    Karnani, Neerja
    Lee, Kirsten
    Lefebvre, Gregory C.
    Navas, Patrick A.
    Neri, Fidencio
    Parker, Stephen C. J.
    Sabo, Peter J.
    Sandstrom, Richard
    Shafer, Anthony
    [J]. NATURE, 2007, 447 (7146) : 799 - 816
  • [3] The Air noncoding RNA:: An imprinted cis-silencing transcript
    Braidotti, G
    Baubec, T
    Pauler, F
    Seidl, C
    Smrzka, O
    Stricker, S
    Yotova, I
    Barlow, DP
    [J]. COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, 2004, 69 : 55 - 66
  • [4] Brennecke J, 2007, CELL, V128, P1089, DOI 10.1016/j.cell.2007.01.043
  • [5] The imprinted H19 noncoding RNA is a primary microRNA precursor
    Cai, Xuezhong
    Cullen, Bryan R.
    [J]. RNA, 2007, 13 (03) : 313 - 316
  • [6] Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs
    Cai, XZ
    Hagedorn, CH
    Cullen, BR
    [J]. RNA, 2004, 10 (12) : 1957 - 1966
  • [7] MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline
    Carmell, Michelle A.
    Girard, Angelique
    van de Kant, Henk J. G.
    Bourc'his, Deborah
    Bestor, Timothy H.
    de Rooij, Dirk G.
    Hannon, Gregory J.
    [J]. DEVELOPMENTAL CELL, 2007, 12 (04) : 503 - 514
  • [8] The transcriptional landscape of the mammalian genome
    Carninci, P
    Kasukawa, T
    Katayama, S
    Gough, J
    Frith, MC
    Maeda, N
    Oyama, R
    Ravasi, T
    Lenhard, B
    Wells, C
    Kodzius, R
    Shimokawa, K
    Bajic, VB
    Brenner, SE
    Batalov, S
    Forrest, ARR
    Zavolan, M
    Davis, MJ
    Wilming, LG
    Aidinis, V
    Allen, JE
    Ambesi-Impiombato, X
    Apweiler, R
    Aturaliya, RN
    Bailey, TL
    Bansal, M
    Baxter, L
    Beisel, KW
    Bersano, T
    Bono, H
    Chalk, AM
    Chiu, KP
    Choudhary, V
    Christoffels, A
    Clutterbuck, DR
    Crowe, ML
    Dalla, E
    Dalrymple, BP
    de Bono, B
    Della Gatta, G
    di Bernardo, D
    Down, T
    Engstrom, P
    Fagiolini, M
    Faulkner, G
    Fletcher, CF
    Fukushima, T
    Furuno, M
    Futaki, S
    Gariboldi, M
    [J]. SCIENCE, 2005, 309 (5740) : 1559 - 1563
  • [9] Purifying mRNAs with a high-affinity eIF4E mutant identifies the short 3′ poly(A) end phenotype
    Choi, YH
    Hagedorn, CH
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (12) : 7033 - 7038
  • [10] Mechanism and regulation of mRNA polyadenylation
    Colgan, DF
    Manley, JL
    [J]. GENES & DEVELOPMENT, 1997, 11 (21) : 2755 - 2766