Mammalian DIS3L2 exoribonuclease targets the uridylated precursors of let-7 miRNAs

It has been known that Lin28 negatively regulates let-7 production by recruiting 3′-terminal uridylyl transferases. As a result, the processing of uridylated pre-let-7 by Dicer is blocked. The identity of the RNase that acts to degrade uridylated pre-let-7 was not known until recently. In this paper, the authors report the identification of mammalian DIS3L2 as an oligo(U)-binding exonuclease that specifically targets uridylated let-7 miRNA precursors in vivo. These findings complement a recent report which identified Dis3l2 as the relevant mouse exonuclease. DIS3L2 has 3′–5′ exonuclease activity, is predominantly cytoplasmic and, unlike other mammalian DIS3 orthologs, is not stably associated with the RNA exosome complex.

[1]  T. Jensen,et al.  Exonuclease hDIS3L2 specifies an exosome‐independent 3′‐5′ degradation pathway of human cytoplasmic mRNA , 2013, The EMBO journal.

[2]  R. Gregory,et al.  A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway , 2013, Nature.

[3]  P. Golik,et al.  The exoribonuclease Dis3L2 defines a novel eukaryotic RNA degradation pathway , 2013, The EMBO journal.

[4]  Hyeshik Chang,et al.  Mono-Uridylation of Pre-MicroRNA as a Key Step in the Biogenesis of Group II let-7 MicroRNAs , 2012, Cell.

[5]  R. Gregory,et al.  Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7). , 2012, RNA.

[6]  C. Eckmann,et al.  Subcellular specialization of multifaceted 3'end modifying nucleotidyltransferases. , 2012, Current opinion in cell biology.

[7]  Michael T. McManus,et al.  Widespread RNA 3'-end oligouridylation in mammals. , 2012, RNA.

[8]  J. Opitz,et al.  Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility , 2012, Nature Genetics.

[9]  T. Jensen,et al.  Interaction profiling identifies the human nuclear exosome targeting complex. , 2011, Molecular cell.

[10]  C. Joo,et al.  Single‐molecule approach to immunoprecipitated protein complexes: insights into miRNA uridylation , 2011, EMBO reports.

[11]  G. M. Wilson,et al.  Different modes of interaction by TIAR and HuR with target RNA and DNA , 2011, Nucleic acids research.

[12]  A. Reymond,et al.  A High-Resolution Anatomical Atlas of the Transcriptome in the Mouse Embryo , 2011, PLoS biology.

[13]  Shimyn Slomovic,et al.  Dis3‐like 1: a novel exoribonuclease associated with the human exosome , 2010, The EMBO journal.

[14]  T. Jensen,et al.  The human core exosome interacts with differentially localized processive RNases: hDIS3 and hDIS3L , 2010, The EMBO journal.

[15]  C. Norbury,et al.  Polyadenylation and beyond: emerging roles for noncanonical poly(A) polymerases , 2010, Wiley interdisciplinary reviews. RNA.

[16]  C. Croce.  Causes and consequences of microRNA dysregulation in cancer , 2009, Nature Reviews Genetics.

[17]  R. Gregory,et al.  Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in embryonic stem cells , 2009, Nature Structural &Molecular Biology.

[18]  C. Joo,et al.  TUT4 in Concert with Lin28 Suppresses MicroRNA Biogenesis through Pre-MicroRNA Uridylation , 2009, Cell.

[19]  D. Tollervey,et al.  The N-terminal PIN domain of the exosome subunit Rrp44 harbors endonuclease activity and tethers Rrp44 to the yeast core exosome , 2009, Nucleic acids research.

[20]  Bertrand Séraphin,et al.  Endonucleolytic RNA cleavage by a eukaryotic exosome , 2008, Nature.

[21]  C. Joo,et al.  Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA. , 2008, Molecular cell.

[22]  F. Slack,et al.  let-7 microRNAs in development, stem cells and cancer. , 2008, Trends in molecular medicine.

[23]  Piotr Sliz,et al.  Determinants of MicroRNA Processing Inhibition by the Developmentally Regulated RNA-binding Protein Lin28* , 2008, Journal of Biological Chemistry.

[24]  E. Conti,et al.  Structure of the active subunit of the yeast exosome core, Rrp44: diverse modes of substrate recruitment in the RNase II nuclease family. , 2008, Molecular cell.

[25]  D. Tollervey,et al.  The exosome subunit Rrp44 plays a direct role in RNA substrate recognition. , 2007, Molecular cell.

[26]  C. Norbury,et al.  Efficient RNA Polyuridylation by Noncanonical Poly(A) Polymerases , 2007, Molecular and Cellular Biology.

[27]  H. Urlaub,et al.  Identification, cloning, and functional analysis of the human U6 snRNA-specific terminal uridylyl transferase. , 2006, RNA.

[28]  E. Petfalski,et al.  RNA Degradation by the Exosome Is Promoted by a Nuclear Polyadenylation Complex , 2005, Cell.

[29]  W. Keller,et al.  A New Yeast Poly(A) Polymerase Complex Involved in RNA Quality Control , 2005, PLoS biology.

[30]  Eric Westhof,et al.  Single Processing Center Models for Human Dicer and Bacterial RNase III , 2004, Cell.

[31]  Alan G Hinnebusch,et al.  Nuclear surveillance and degradation of hypomodified initiator tRNAMet in S. cerevisiae. , 2004, Genes & development.

[32]  J. G. McAfee,et al.  Oligonucleotide binding specificities of the hnRNP C protein tetramer. , 1998, Nucleic acids research.

[33]  J. E. Stefano.  Purified lupus antigen la recognizes an oligouridylate stretch common to the 3′ termini of RNA polymerase III transcripts , 1984, Cell.

[34]  Michael K. Slevin,et al.  mRNAs containing the histone 3' stem-loop are degraded primarily by decapping mediated by oligouridylation of the 3' end. , 2013, RNA.

[35]  C. Norbury,et al.  The human cytoplasmic RNA terminal U-transferase ZCCHC11 targets histone mRNAs for degradation. , 2011, RNA.

[36]  B. Séraphin,et al.  A single subunit, Dis3, is essentially responsible for yeast exosome core activity , 2007, Nature Structural &Molecular Biology.