THE SIGNAL RECOGNITION PARTICLE RECEPTOR-ALPHA SUBUNIT ASSEMBLES CO-TRANSLATIONALLY ON THE ENDOPLASMIC-RETICULUM MEMBRANE DURING AN MESSENGER-RNA-ENCODED TRANSLATION PAUSE IN-VITRO
Jc. Young et Dw. Andrews, THE SIGNAL RECOGNITION PARTICLE RECEPTOR-ALPHA SUBUNIT ASSEMBLES CO-TRANSLATIONALLY ON THE ENDOPLASMIC-RETICULUM MEMBRANE DURING AN MESSENGER-RNA-ENCODED TRANSLATION PAUSE IN-VITRO, EMBO journal, 15(1), 1996, pp. 172-181
Many proteins, including the alpha subunit of the signal recognition p
article receptor (SR alpha), are targeted within the cell by poorly de
fined mechanisms. A 140 residue N-terminal domain of SR alpha targets
and anchors the polypeptide to the endoplasmic reticulum membrane by a
mechanism independent of the pathway involving the signal recognition
particle. To investigate the mechanism of membrane anchoring, transla
tion pause sites on the SR alpha mRNA were used to examine the targeti
ng of translation intermediates. A strong pause site at nucleotide 507
of the mRNA open reading frame corresponded with the shortest nascent
SR alpha polypeptide able to assemble on membranes, An mRNA sequence
at this pause site that resembles a class of viral -1 frameshift seque
nces caused translation pausing when transferred into another mRNA con
text, Site-directed mutagenesis of the mRNA greatly reduced translatio
n pausing without altering the polypeptide sequence, demonstrating una
mbiguously a role for this mRNA sequence in translation pausing. SR al
pha polypeptides synthesized from the non-pausing mRNA were impaired i
n co-translational membrane anchoring, Furthermore, co-translational m
embrane assembly of SR alpha appears to anchor polysomes translating S
R alpha to membranes.