How does an mRNA find its way? Intracellular localisation of transcripts

Abstract

The localisation of transcripts to specific regions of the cell probably occurs in all cell types and has many distinct functions that go from the control of body axis formation to learning and memory. mRNAs can be localised by a variety of mechanisms including local protection from degradation, diffusion to a localised anchor, and active transport by motor proteins along the cytoskeleton. In this review, I consider the evidence for each of these mechanisms using a limited, but illustrative, number of examples of localised mRNAs.

Fig. 1

(A–D) Mechanisms of mRNA localization. (A) Diffusion and entrapment: diffusion (facilitated by cytoplasmic flows (blue spiral)) through the cytoplasm and entrapment by a specific anchor (red). (B) Localised degradation and protection: although nothing is known about the nature of the protecting machinery (green), the degradation of hsp83 mRNA is mediated by Smaug and the CCR4/POP2/NOT deadenylase complex (blue). (C) Local synthesis: the local transcription of AChR mRNAs at the neuromuscular junction (NMJ) – regulated by locally acting factors from the nerve and the muscle (yellow arrows) – allows the local accumulation of the receptors. (D) Active transport by motor proteins: bcd and grk mRNAs seem to be transported by dynein to the anterior pole of the oocyte along an anteriorly nucleated population of MTs (blue). Once at the anterior, grk RNA shifts to another population of MTs (red) that mediates its dynein-dependent localisation to the anterior-dorsal corner. In the same cell, osk RNA accumulates at the posterior pole in a KHC-dependent manner, likely by the active transport of the transcript by the motor from the minus ends (at the anterior and cortex, green MTs) to the plus-ends. (E) The nuclear history of a transcript is important for its cytoplasmic localisation. osk mRNA is transcribed in and exported from the nurse cell (NC) nuclei, transported from the NC into the oocyte and finally localised to the posterior. The splicing of osk mRNA and its interaction in the nucleus with several factors, is essential for its localisation. The assembly probably starts by the co-transcriptional binding of Hrp48, and upon splicing, the EJC. Barentsz recognises the complex as it is exported from the nucleus by interaction with eIF4AIII, and finally, Stau joins in the cytoplasm of the NCs. The osk particle moves then from the NCs into the oocyte where presumably by interacting with the KHC, it localises to the posterior pole. (F) Remodeling of the localising complex is probably an essential step in RNA localisation. As shown in the localisation of Vg1 RNA in the Xenopus oocyte, hnRNP I and Vg1RBP/Vera bind directly to each other and to the transcript in the nucleus. Upon export, the complex is remodeled such that these two proteins no longer interact and additional factors become part of the localisation complex, such as Stau and Prrp. The transport of Vg1 mRNA to the vegetal pole is then somehow mediated by a mechanism that seems to require kinesin I and II. NPC: nuclear pore complex; RC: ring canal.