Cotranscription and intergenic splicing of human galactose-1-phosphate uridylyltransferase and interleukin-11 receptor alpha-chain genes generate a fusion mRNA in normal cells. Implication for the production of multidomain proteins during evolution.
In the past 10 years, much attention has been focused on transcription preinitiation complex formation as a target for regulating gene expression, and other targets such as transcription termination complex assemblage have been less intensively investigated. We established the existence of poly(A) site choice and fusion splicing of two adjacent genes, galactose-1-phosphate uridylyltransferase (GALT) and interleukin-11 receptor alpha-chain (IL-11Ralpha), in normal human cells. This 16-kilobase (kb) transcription unit contains two promoters (the first one is constitutive, and the second one, 8 kb downstream, is highly regulated) and two cleavage/polyadenylation signals separated by 12 kb. The promoter from the GALT gene yields two mRNAs, a 1.4-kb mRNA encoding GALT and a 3-kb fusion mRNA when the first poly(A) site is spliced out and the second poly(A) is used. The 3-kb mRNA codes for a fusion protein of unknown function, containing part of the GALT protein and the entire IL-11Ralpha protein. The GALT promoter/IL-11Ralpha poly(A) transcript results from leaky termination and alternative splicing. This feature of RNA polymerase (pol) II transcription, which contrasts with efficient RNA pol I and pol III termination, may be involved, together with chromosome rearrangements, in the generation of fusion proteins with multiple domains and would have major evolutionary implications in terms of natural processes to generate novel proteins with common motifs. Our results, together with accumulation of genomic informations, will stimulate new considerations and experiments in gene expression studies.
Magrangeas
F
F
INSERM U463, 44035 Nantes, France.
Pitiot
G
G
Dubois
S
S
Bragado-Nilsson
E
E
Chérel
M
M
Jobert
S
S
Lebeau
B
B
Boisteau
O
O
Lethé
B
B
Mallet
J
J
Jacques
Y
Y
Minvielle
S
S
D000818:Animals; D019556:COS Cells; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D019143:Evolution, Molecular; D006801:Humans; D053703:Interleukin-11 Receptor alpha Subunit; D011401:Promoter Regions, Genetic; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics*; D053702:Receptors, Interleukin-11; D014158:Transcription, Genetic; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000235:genetics*
C508428:IL11RA protein, human; D053703:Interleukin-11 Receptor alpha Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053702:Receptors, Interleukin-11; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase