Evidence for transcript networks composed of chimeric RNAs in human cells
Sarah Djebali
(1)
,
Julien Lagarde
(1)
,
Philipp Kapranov
(2)
,
Vincent Lacroix
(1)
,
Christelle Borel
(3)
,
Jonathan M. Mudge
(4)
,
Cédric Howald
(5)
,
Sylvain Foissac
(6, 1, 2)
,
Catherine Ucla
(3)
,
Jacqueline Chrast
(5)
,
Paolo Ribeca
(1)
,
David Martin
(1)
,
Ryan R Murray
(7)
,
Xinping Yang
(7)
,
Lila Ghamsari
(7)
,
Chenwei Lin
(7)
,
Ian Bell
(2)
,
Erica Dumais
(2)
,
Jorg Drenkow
(8)
,
Michael L Tress
(8)
,
Josep Lluís Gelpí
(9)
,
Modesto Orozco
(9)
,
Alfonso Valencia
(8)
,
Nynke L van Berkum
(10)
,
Bryan R Lajoie
(10)
,
Marc Vidal
(7)
,
John Stamatoyannopoulos
(11)
,
Philippe Batut
(8)
,
Alex Dobin
(8)
,
Jennifer Harrow
(4)
,
Tim Hubbard
(4)
,
Job Dekker
(10)
,
Adam Frankish
(4)
,
Kourosh Salehi-Ashtiani
(7, 12)
,
Alexandre Reymond
(5)
,
Stylianos E Antonarakis
(3)
,
Roderic Guigó
(1, 12)
,
Thomas R Gingeras
(2, 8)
1
IGDR -
Institut de Génétique et Développement de Rennes
2 UPF - Universitat Pompeu Fabra [Barcelona]
3 Affymetrix Inc.
4 HUG - Geneva University Hospital
5 The Wellcome Trust Sanger Institute [Cambridge]
6 LGC - Laboratoire de Génétique Cellulaire
7 UNIL - Université de Lausanne = University of Lausanne
8 Dana-Farber Cancer Institute [Boston]
9 Harvard University
10 Cold Spring Harbor Laboratory
11 Spanish National Cancer Research Centre
12 University of Barcelona
2 UPF - Universitat Pompeu Fabra [Barcelona]
3 Affymetrix Inc.
4 HUG - Geneva University Hospital
5 The Wellcome Trust Sanger Institute [Cambridge]
6 LGC - Laboratoire de Génétique Cellulaire
7 UNIL - Université de Lausanne = University of Lausanne
8 Dana-Farber Cancer Institute [Boston]
9 Harvard University
10 Cold Spring Harbor Laboratory
11 Spanish National Cancer Research Centre
12 University of Barcelona
Julien Lagarde
- Fonction : Auteur
- PersonId : 755946
- IdRef : 130610062
Vincent Lacroix
- Fonction : Auteur
- PersonId : 178908
- IdHAL : vincent-lacroix
- ORCID : 0000-0002-4235-8524
- IdRef : 130859583
Sylvain Foissac
- Fonction : Auteur
- PersonId : 744914
- IdHAL : sylvainfoissac
- ORCID : 0000-0002-2631-5356
- IdRef : 085595896
David Martin
- Fonction : Auteur
- PersonId : 739074
- IdHAL : david-martin
- ORCID : 0000-0002-3257-9876
Marc Vidal
- Fonction : Auteur
- PersonId : 756524
- ORCID : 0000-0003-3391-5410
Résumé
The classic organization of a gene structure has followed the Jacob and Monod bacterial gene model proposed more than 50 years ago. Since then, empirical determinations of the complexity of the transcriptomes found in yeast to human has blurred the definition and physical boundaries of genes. Using multiple analysis approaches we have characterized individual gene boundaries mapping on human chromosomes 21 and 22. Analyses of the locations of the 5' and 3' transcriptional termini of 492 protein coding genes revealed that for 85% of these genes the boundaries extend beyond the current annotated termini, most often connecting with exons of transcripts from other well annotated genes. The biological and evolutionary importance of these chimeric transcripts is underscored by (1) the non-random interconnections of genes involved, (2) the greater phylogenetic depth of the genes involved in many chimeric interactions, (3) the coordination of the expression of connected genes and (4) the close in vivo and three dimensional proximity of the genomic regions being transcribed and contributing to parts of the chimeric RNAs. The non-random nature of the connection of the genes involved suggest that chimeric transcripts should not be studied in isolation, but together, as an RNA network.