Chromosome fusions triggered by noncoding RNA.
Chromosomal fusions are common in normal and cancer cells and can produce aberrant gene products that promote transformation. The mechanisms driving these fusions are poorly understood, but recurrent fusions are widespread. This suggests an underlying mechanism, and some authors have proposed a possible role for RNA in this process. The unicellular eukaryote Oxytricha trifallax displays an exorbitant capacity for natural genome editing, when it rewrites its germline genome to form a somatic epigenome. This developmental process provides a powerful model system to directly test the influence of small noncoding RNAs on chromosome fusion events during somatic differentiation. Here we show that small RNAs are capable of inducing chromosome fusions in 4 distinct cases (out of 4 tested), including one fusion of 3 chromosomes. We further show that these RNA-mediated chromosome fusions are heritable over multiple sexual generations and that transmission of the acquired fusion is associated with endogenous production of novel piRNA molecules that target the fused junction. We also demonstrate the capacity of a long noncoding RNA (lncRNA) to induce chromosome fusion of 2 distal germline loci. These results underscore the ability of short-lived, aberrant RNAs to act as drivers of chromosome fusion events that can be stably transmitted to future generations.
a Department of Biology , American University , Washington, DC , USA.
John R
JR
Bracht
b Department of Chemistry & Chemical Biology , Rensselaer Polytechnic Institute Troy , NY , USA.
Xing
X
Wang
c Department of Molecular Biology , Princeton University , Princeton , NJ , USA.|d Department of Immunobiology , Yale University , New Haven , CT , USA.
Keerthi
K
Shetty
c Department of Molecular Biology , Princeton University , Princeton , NJ , USA.
Xiao
X
Chen
a Department of Biology , American University , Washington, DC , USA.
Grace J
GJ
Uttarotai
a Department of Biology , American University , Washington, DC , USA.
Evan C
EC
Callihan
c Department of Molecular Biology , Princeton University , Princeton , NJ , USA.
Sierra S
SS
McCloud
c Department of Molecular Biology , Princeton University , Princeton , NJ , USA.
Derek M
DM
Clay
e Department of Ecology & Evolutionary Biology , Princeton University , NJ , USA.
Jingmei
J
Wang
f Institute of Cell Biology, University of Bern , Switzerland.
Mariusz
M
Nowacki
e Department of Ecology & Evolutionary Biology , Princeton University , NJ , USA.|g Departments of Biochemistry & Molecular Biophysics and Biological Sciences , Columbia University , NY , USA.
Laura F
LF
Landweber
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002875:Chromosomes / Q000235:genetics / Q000378:metabolism*; D015321:Gene Rearrangement / Q000502:physiology*; D056426:Genetic Loci; D018503:Genome, Protozoan; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008845:Microinjections; D016813:Oxytricha / Q000235:genetics*; D016053:RNA, Protozoan / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA / Q000379:methods
D016053:RNA, Protozoan; D034741:RNA, Small Interfering; D022661:RNA, Untranslated
Chromosome fusion; Oxytricha; long noncoding RNA; piRNAs