Characterization of SRp46, a novel human SR splicing factor encoded by a PR264/SC35 retropseudogene.
The highly conserved SR family contains a growing number of phosphoproteins acting as both essential and alternative splicing factors. In this study, we have cloned human genomic and cDNA sequences encoding a novel SR protein designated SRp46. Nucleotide sequence analyses have revealed that the SRp46 gene corresponds to an expressed PR264/SC35 retropseudogene. As a result of mutations and amplifications, the SRp46 protein significantly differs from the PR264/SC35 factor, mainly at the level of its RS domain. Northern and Western blot analyses have established that SRp46 sequences are expressed at different levels in several human cell lines and normal tissues, as well as in simian cells. In contrast, sequences homologous to SRp46 are not present in mice. In vitro splicing studies indicate that the human SRp46 recombinant protein functions as an essential splicing factor in complementing a HeLa cell S100 extract deficient in SR proteins. In addition, complementation analyses performed with beta-globin or adenovirus E1A transcripts and different splicing-deficient extracts have revealed that SRp46 does not display the same activity as PR264/SC35. These results demonstrate, for the first time, that an SR splicing factor, which represents a novel member of the SR family, is encoded by a functional retropseudogene.
Laboratoire d'Oncologie Virale et Moléculaire, INSERM U142, Bâtiment Kourilsky, Hôpital Saint-Antoine, Paris 75571 Cedex 12, France.
J
J
Soret
R
R
Gattoni
C
C
Guyon
A
A
Sureau
M
M
Popielarz
E
E
Le Rouzic
S
S
Dumon
F
F
Apiou
B
B
Dutrillaux
H
H
Voss
W
W
Ansorge
J
J
Stévenin
B
B
Perbal
D016475:3T3 Cells; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D018076:DNA, Complementary; D015870:Gene Expression; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics*; D011544:Pseudogenes; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D000068103:Serine-Arginine Splicing Factors
D018076:DNA, Complementary; D010750:Phosphoproteins; C000595776:SRSF8 protein, human; D000068103:Serine-Arginine Splicing Factors