SMN protein promotes membrane compartmentalization of ribosomal protein S6 transcript in human fibroblasts

Francesca Gabanella,Claudio Passananti,Massimo Ralli,Antonio Greco,Annalisa Onori,Maria Grazia Di Certo

doi:10.1038/s41598-020-76174-3

Francesca Gabanella, Claudio Passananti + Show 4 more

Open Access

https://doi.org/10.1038/s41598-020-76174-3

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Abstract

Alterations of RNA homeostasis can lead to severe pathological conditions. The Survival of Motor Neuron (SMN) protein, which is reduced in Spinal Muscular Atrophy, impacts critical aspects of the RNA life cycle, such as splicing, trafficking, and translation. Increasing evidence points to a potential role of SMN in ribosome biogenesis. Our previous study revealed that SMN promotes membrane-bound ribosomal proteins (RPs), sustaining activity-dependent local translation. Here, we suggest that plasma membrane domains could be a docking site not only for RPs but also for their encoding transcripts. We have shown that SMN knockdown perturbs subcellular localization as well as translation efficiency of RPS6 mRNA. We have also shown that plasma membrane-enriched fractions from human fibroblasts retain RPS6 transcripts in an SMN-dependent manner. Furthermore, we revealed that SMN traffics with RPS6 mRNA promoting its association with caveolin-1, a key component of membrane dynamics. Overall, these findings further support the SMN-mediated crosstalk between plasma membrane dynamics and translation machinery. Importantly, our study points to a potential role of SMN in the ribosome assembly pathway by selective RPs synthesis/localization in both space and time.

Highlights

Alterations of RNA homeostasis can lead to severe pathological conditions
It is required for resolving transcription termination r egions[26]. It facilitates the assembly of distinct RNPs, such as small nuclear RNPs, small nucleolar RNPs, and small Cajal body RNPs27,28 and it promotes assembly and trafficking of messenger ribonucleoprotein complexes[29]
We showed that Survival of Motor Neuron (SMN) coexists with ribosomal proteins (RPs) in caveolin-rich membrane domains and promotes spatially restricted protein production underlying membrane remodelling[14]

Summary

Introduction

Alterations of RNA homeostasis can lead to severe pathological conditions. The Survival of Motor Neuron (SMN) protein, which is reduced in Spinal Muscular Atrophy, impacts critical aspects of the RNA life cycle, such as splicing, trafficking, and translation. Our previous study revealed that SMN promotes membrane-bound ribosomal proteins (RPs), sustaining activity-dependent local translation. We revealed that SMN traffics with RPS6 mRNA promoting its association with caveolin-1, a key component of membrane dynamics. It is reasonable to suppose that membrane dynamics may influence RNA homeostasis as well as mRNA translation underlying specialized subcellular activities In this framework, RNA-related proteins may be key determinants dictating the proteome profile in time and space. For the first time we have obtained a spatial mapping of RPS6 mRNA in single cells by using the target RNA-initiated rolling circle amplification method These findings confirm the intriguing relationship between membrane trafficking and the translation pathway. This study suggests that SMN could mediate peripheral localization of a subset of RP-coding transcripts, contributing in this way to select protein synthesis in time and space

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