title: Identification and validation of a novel mature microRNA encoded by the Merkel cell polyomavirus in human Merkel cell carcinomas.
abstract: BACKGROUND
  Merkel cell polyomavirus (MCPyV) is present in approximately 80% of human Merkel cell carcinomas (MCCs). A previous in silico prediction suggested MCPyV encodes a microRNA (miRNA) that may regulate cellular and viral genes.
  
  
  OBJECTIVE
  To determine the presence and prevalence of a putative MCPyV-encoded miRNA in human MCC tumors.
  
  
  METHODS
  Over 30 million small RNAs from 7 cryopreserved MCC tumors and 1 perilesional sample were sequenced. 45 additional MCC tumors were examined for expression of an MCPyV-encoded mature miRNA by reverse transcription real-time PCR.
  
  
  RESULTS
  An MCPyV-encoded mature miRNA, "MCV-miR-M1-5p", was detected by direct sequencing in 2 of 3 MCPyV-positive MCC tumors. Although a precursor miRNA, MCV-miR-M1, had been predicted in silico and studied in vitro by Seo et al., no MCPyV-encoded miRNAs have been directly detected in human tissues. Importantly, the mature sequence of MCV-miR-M1 found in vivo was identical in all 79 reads obtained but differed from the in silico predicted mature miRNA by a 2-nucleotide shift, resulting in a distinct seed region and a different set of predicted target genes. This mature miRNA was detected by real-time PCR in 50% of MCPyV-positive MCCs (n = 38) and in 0% of MCPyV-negative MCCs (n = 13).
  
  
  CONCLUSIONS
  MCV-miR-M1-5p is expressed at low levels in 50% of MCPyV-positive MCCs. This virus-encoded miRNA is predicted to target genes that may play a role in promoting immune evasion and regulating viral DNA replication.
authors: Department of Medicine/Dermatology, University of Washington, Seattle, WA 98109, USA.
authors: Sherry
authors: S
authors: Lee
authors: Kelly G
authors: KG
authors: Paulson
authors: Elizabeth P
authors: EP
authors: Murchison
authors: Olga K
authors: OK
authors: Afanasiev
authors: Can
authors: C
authors: Alkan
authors: J Helen
authors: JH
authors: Leonard
authors: David R
authors: DR
authors: Byrd
authors: Gregory J
authors: GJ
authors: Hannon
authors: Paul
authors: P
authors: Nghiem
mesh_terms: D001483:Base Sequence; D015266:Carcinoma, Merkel Cell / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral / Q000096:biosynthesis; D006801:Humans; D059965:Merkel cell polyomavirus / Q000235:genetics*; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D027601:Polyomavirus Infections / Q000235:genetics / Q000473:pathology / Q000821:virology*; D012367:RNA, Viral / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D016415:Sequence Alignment; D017423:Sequence Analysis, RNA
chemical_list: D004279:DNA, Viral; D035683:MicroRNAs; D012367:RNA, Viral