Human ribosomal RNA gene arrays display a broad range of palindromic structures.
The standard model of eukaryotic ribosomal RNA (rRNA) genes involves tandem arrays with hundreds of units in clusters, the nucleolus organizer regions (NORs). A first genomic overview for human cells is reported here for these regions, which have never been sequenced in their totality, by using molecular combing. The rRNA-coding regions are examined by fluorescence on single molecules of DNA with two specific probes that cover their entire length. The standard organization assumed for rDNA units is a transcribed region followed by a nontranscribed spacer. While we confirmed this arrangement in many cases, unorthodox patterns were also observed in normal individuals, with one-third of the rDNA units rearranged to form apparently palindromic structures (noncanonical units) independent of the age of the donors. In cells from individuals with a deficiency in the WRN RecQ helicase (Werner syndrome), the proportion of palindromes increased to one-half. These findings, supported by Southern blot analyses, show that rRNA genes are a mosaic of canonical and (presumably nonfunctional) palindromic units that may be altered by factors associated with genomic instability and pathology.
Caburet
Sandrine
S
Unité de Stabilité des Génomes, Institut Pasteur, 75724 Paris, France.
Conti
Chiara
C
Schurra
Catherine
C
Lebofsky
Ronald
R
Edelstein
Stuart J
SJ
Bensimon
Aaron
A
D015139:Blotting, Southern; D002478:Cells, Cultured; D015342:DNA Probes; D023061:Gene Order; D015321:Gene Rearrangement; D020459:Genes, rRNA / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D009690:Nucleic Acid Conformation; D012335:RNA, Ribosomal / Q000737:chemistry; D014898:Werner Syndrome / Q000235:genetics*
D015342:DNA Probes; D012335:RNA, Ribosomal