Altered expression of heterogenous nuclear ribonucleoproteins and SR factors in human colon adenocarcinomas.
Alternative splicing is part of the expression program of a wide number of genes implicated in cell growth and differentiation. Although the occurrence of inappropriate alternative splicing in tumors has started to emerge, the underlying molecular mechanisms have been, thus far, largely unexplored. We have investigated the alternative splicing pattern of the CD44 gene in specimens of nonfamilial colon adenocarcinomas at different stages of tumor progression. In the same patients, we have assessed by Northern blotting analysis the mRNA levels of different heterogeneous nuclear ribonucleoproteins and SR factors, all involved in pre-mRNA splicing and, more in general, in mRNA maturation. The results of this analysis highlight a general rule for the mode of splicing of the CD44 pre-mRNA. Moreover, we found that the mRNA levels of different SR proteins in tumor specimens are different from, and usually lower than, those detected in samples of nonpathological tissue adjacent to the tumor. Quantitative analysis demonstrates that, in tumors, the mRNA levels of ASF, SRp40, SRp55, and SRp75, when normalized to those of heterogeneous nuclear ribonucleoprotein A1, are lower than those of SRp20 and SRp30. Interestingly, this reduction is more drastic in patients showing a more altered CD44 splicing pattern and seems to be related to the propensity to develop metastases.
Ghigna
C
C
Istituto di Genetica Biochimica ed Evoluzionistica Consiglio Nazionale delle Ricerche, Università di Pavia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Italy.
Moroni
M
M
Porta
C
C
Riva
S
S
Biamonti
G
G
D000230:Adenocarcinoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D003110:Colonic Neoplasms / Q000378:metabolism*; D005260:Female; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors
D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C000619656:hnRNPA1 protein, human; D000068103:Serine-Arginine Splicing Factors