Single translation--dual destination: mechanisms of dual protein targeting in eukaryotes

Abstract

It is well documented that single eukaryotic genes can give rise to proteins that are localized to several subcellular locations. This is achieved at the level of transcription, splicing and translation, and results in two or more translation products that either harbour or lack specific targeting signals. Nevertheless, the possibility of dual targeting of a single translation product has recently emerged. Here, we review cases of such dual targeting with emphasis on the mechanisms through which these phenomena occur. Proteins that harbour one signal, two separate signals or an overlapping ambiguous signal may follow dual distribution in the cell. The mechanism of dual targeting is driven by the competition or promiscuity of various molecular events. Protein folding, post-translational modification and protein-protein interaction are key players in this phenomenon.

Figure 1

Mechanisms by which proteins with identical activities are distributed in the eukaryotic cell. (A) mRNA molecules transcribed from two genes, of which only one carries an organelle targeting sequence (TS, shown in green). (B) Two mRNAs are transcribed from one gene, but only one encodes a TS. (C) A non-spliced mRNA and the spliced mRNA (TS lost) encode products in the organelle and in the rest of the cell, respectively. (D) A single message is translated from alternative initiation codons to produce TS-containing and TS-lacking products. (E) A single translation product containing the TS is nevertheless distributed between the organelle and the rest of the cell by mechanisms described in this review.

Figure 2

'Tricks' used for dual distribution: proteins can undergo dual distribution in the eukaryotic cell by using a combination of various processes described in detail in the text. (A) Competition between two signals on the same polypeptide. (B) An ambiguous signal that is recognized by two organelles. (C) Inaccessibility of a signal by (i) folding, (ii) protein binding, and (iii) modification of the distributed polypeptide. (D) Incomplete import and (E) retrograde translocation. Possible mechanisms based on either release by membrane leakage (F), or export of proteins from organelles (G) are indicated in grey.