Multiple protein 4.1 isoforms produced by alternative splicing in human erythroid cells.
Protein 4.1 is a multifunctional structural protein located in the erythrocyte membrane skeleton and in many nonerythroid cells. Molecular characterization of cloned protein 4.1 sequences from human reticulocytes has revealed the existence of multiple transcripts of the protein 4.1 gene that may encode a family of closely related protein isoforms. Several independently isolated cDNAs were sequenced and demonstrated to encode four different protein 4.1 species having identical primary sequences, except for the presence or absence of discrete peptides in the 8-kDa spectrin/actin binding domain (21 amino acids) and near the carboxyl terminus (43 and 34 amino acids). The same four protein 4.1 isoforms were detected when reticulocyte protein 4.1 mRNA sequences were reverse transcribed into cDNA and enzymatically amplified in vitro by using protein 4.1-specific oligonucleotide primers and the polymerase chain reaction. The finding of multiple protein 4.1 isoforms raises the possibility that the many binding functions ascribed to protein 4.1 may reside in distinct structural isoforms. Since only a single protein 4.1 gene appears to be expressed in erythrocytes, it is likely that these isoforms are produced by alternative mRNA splicing from a common protein 4.1 pre-mRNA. Multiple RNA splicing pathways are thus operative in the protein 4.1 gene even within a single cell lineage, human erythroid cells.
Conboy
J G
JG
Department of Laboratory Medicine, University of California, San Francisco 94143.
Chan
J
J
Mohandas
N
N
Kan
Y W
YW
D000595:Amino Acid Sequence; D000755:Anemia, Sickle Cell / Q000097:blood / Q000235:genetics; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins; D004247:DNA / Q000097:blood / Q000235:genetics; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009479:Neuropeptides; D012326:RNA Splicing; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics*; D012156:Reticulocytes / Q000378:metabolism
D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1; D004247:DNA