Characterization of novel elongated Parvulin isoforms that are ubiquitously expressed in human tissues and originate from alternative transcription initiation.
BACKGROUND
The peptidyl prolyl cis/trans isomerase (PPIase) Parvulin (Par14/PIN4) is highly conserved in all metazoans and is assumed to play a role in cell cycle progression and chromatin remodeling. It is predominantly localized to the nucleus and binds to chromosomal DNA as well as bent oligonucleotides in vitro.


RESULTS
In this study we confirm by RT-PCR the existence of a longer Parvulin isoform expressed in all tissues examined so far. This isoform contains a 5' extension including a 75 bp extended open reading frame with two coupled SNPs leading to amino acid substitutions Q16R and R18S. About 1% of all Parvulin mRNAs include the novel extension as quantified by real-time PCR. The human Parvulin promoter is TATA-less and situated in a CpG island typical for house keeping genes. Thus, different Parvulin mRNAs seem to arise by alternative transcription initiation. N-terminally extended Parvulin is protected from rapid proteinaseK degradation. In HeLa and HepG2 cell lysates two protein species of about 17 and 28 KDa are detected by an antibody against an epitope within the N-terminal extension. These two bands are also recognized by an antibody towards the PPIase domain of Parvulin. The longer Parvulin protein is encoded by the human genome but absent from rodent, bovine and non-mammalian genomes.


CONCLUSIONS
Due to its molecular weight of 16.6 KDa we denote the novel Parvulin isoform as Par17 following the E. coli Par10 and human Par14 nomenclature. The N-terminal elongation of Par17-QR and Par17-RS suggests these isoforms to perform divergent functions within the eukaryotic cell than the well characterized Par14.
Mueller
Jonathan Wolf
JW
Department Structural and Medicinal Biochemistry, Center for Medical Biotechnology-ZMB, University of Duisburg and Essen, 45117 Essen, Germany. jonathan.mueller@uni-due.de
Kessler
Daniel
D
Neumann
Daniel
D
Stratmann
Tina
T
Papatheodorou
Panagiotis
P
Hartmann-Fatu
Cristina
C
Bayer
Peter
P
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D029968:Escherichia coli Proteins; D006801:Humans; D008969:Molecular Sequence Data; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D016415:Sequence Alignment; D014018:Tissue Distribution; D024363:Transcription Initiation Site
D029968:Escherichia coli Proteins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D020033:Protein Isoforms; D012333:RNA, Messenger; C000606846:PIN1 protein, human; C000606848:PIN4 protein, human; D019696:Peptidylprolyl Isomerase; C000606851:parvA protein, E coli