Translational regulation of the immunoglobulin heavy-chain binding protein mRNA.
Translation of the mRNA encoding the immunoglobulin heavy-chain binding protein (BiP) is enhanced in poliovirus-infected cells at a time when translation of host cell mRNAs is inhibited. To test whether the mRNA of BiP is translated by internal ribosome binding, like picornaviral RNAs, we constructed plasmids for the expression of dicistronic hybrid RNAs containing the 5' noncoding region (5'NCR) of BiP as an intercistronic spacer element between two cistrons. Expression of these dicistronic mRNAs in mammalian cells resulted in efficient translation of both cistrons, demonstrating that the 5'NCR of BiP can confer internal ribosome binding to a heterologous RNA. This result suggests that the mRNA encoding BiP is bifunctional and can be translated by an internal ribosome-binding mechanism, in addition to the conventional cap-dependent scanning mechanism. This is the first demonstration of a cellular mRNA that can be translated by internal ribosome binding, and implies that this may be a mechanism for cellular translational regulation.
Macejak
D G
DG
Department of Biochemistry, Biophysics and Genetics, University of Colorado Health Sciences Center, Denver.
Sarnow
P
P
D002352:Carrier Proteins / Q000235:genetics*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006367:HeLa Cells; D006360:Heat-Shock Proteins; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D018832:Molecular Chaperones; D010442:Peptide Chain Initiation, Translational; D011051:Poliomyelitis; D012333:RNA, Messenger / Q000235:genetics*; D011993:Recombinant Fusion Proteins; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012270:Ribosomes / Q000378:metabolism; D014162:Transfection
D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D007143:Immunoglobulin Heavy Chains; D018832:Molecular Chaperones; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins