The Identification and Functional Analysis of mRNA Localizing to Centrosomes

Abstract

Centrosomes are multifunctional organelles tasked with organizing the microtubule cytoskeleton required for genome stability, intracellular trafficking, and ciliogenesis. Contributing to the diversity of centrosome functions are cell cycle-dependent oscillations in protein localization and post-translational modifications. Less understood is the role of centrosome-localized messenger RNA (mRNA). Since its discovery, the concept of nucleic acids at the centrosome was controversial, and physiological roles for centrosomal mRNAs remained muddled and underexplored. Over the past decades, however, transcripts, RNA-binding proteins, and ribosomes were detected at the centrosome in various organisms and cell types, hinting at a conservation of function. Indeed, recent work defines centrosomes as sites of local protein synthesis, and defined mRNAs were recently implicated in regulating centrosome functions. In this review, we summarize the evidence for the presence of mRNA at the centrosome and the current work that aims to unravel the biological functions of mRNA localized to centrosomes.

Keywords: MTOC; RNA localization; centrosome; co-translational tranport; local translation; mRNA; post-transcriptional regulation.

FIGURE 1

The centrosome as a center for translational control. (A) Cartoon schematic of centrosome organization showing a central pair of centrioles (magenta) with 9-fold radial symmetry of microtubule triplets surrounded by subconcentric rings of PCM (yellow and orange toroids). Microtubule filaments (green lines) are anchored with their minus-ends docked within γ-tubulin ring complexes (grey circles) embedded within the PCM. A model mRNA (black) recognized by RNA-binding proteins (stars) binding to its 3′-untranslated region (UTR; brown box) is shown undergoing active translation by ribosomes (purple circles). Nascent peptides (fiery ribbons) emerge near the centrosome. Note, objects are not drawn to scale. (B) Image shows single molecule fluorescence in situ hybridization for plp mRNA (green) in a prophase (DNA, magenta) syncytial Drosophila embryo. plp mRNA coalesces around centrosomes (yellow). Image below shows an inverted display of the mRNA channel to maximize contrast. Bar: 5 μm. Image courtesy of Dr. Junnan Fang, Ph.D.

FIGURE 2

Cell cycle-dependent variances in mRNA distributions. Illustration of differential mRNA distributions of conserved centrosome-enriched mRNAs during interphase, prophase, and metaphase-to-late mitosis (metaphase (+)). Below, a graphical summary of mRNA distributions at the same cell cycle stages as reported by (Sepulveda et al., 2018; Ryder et al., 2020; Safieddine et al., 2021). The size and intensity of the circle correlates with the prevalence of mRNA localization; representative mRNAs are listed.