Ribosome-membrane crosstalk: Co-translational targeting pathways of proteins across membranes in prokaryotes and eukaryotes.

Ribosomes are the molecular machine of living cells designed for decoding mRNA-encoded genetic information into protein. Being sophisticated machinery, both in design and function, the ribosome not only carries out protein synthesis, but also coordinates several other ribosome-associated cellular processes. One such process is the translocation of proteins across or into the membrane depending on their secretory or membrane-associated nature. These proteins comprise a large portion of a cell's proteome and act as key factors for cellular survival as well as several crucial functional pathways. Protein transport to extra- and intra-cytosolic compartments (across the eukaryotic endoplasmic reticulum (ER) or across the prokaryotic plasma membrane) or insertion into membranes majorly occurs through an evolutionarily conserved protein-conducting channel called translocon (eukaryotic Sec61 or prokaryotic SecYEG channels). Targeting proteins to the membrane-bound translocon may occur via post-translational or co-translational modes and it is often mediated by recognition of an N-terminal signal sequence in the newly synthesizes polypeptide chain. Co-translational translocation is coupled to protein synthesis where the ribosome-nascent chain complex (RNC) itself is targeted to the translocon. Here, in the light of recent advances in structural and functional studies, we discuss our current understanding of the mechanistic models of co-translational translocation, coordinated by the actively translating ribosomes, in prokaryotes and eukaryotes.