High-affinity RNA targets of the Survival Motor Neuron protein reveal diverse preferences for sequence and structural motifs

Nucleic Acids Research
Eric W OttesenRavindra N Singh

Abstract

The Survival Motor Neuron (SMN) protein is essential for survival of all animal cells. SMN harbors a nucleic acid-binding domain and plays an important role in RNA metabolism. However, the RNA-binding property of SMN is poorly understood. Here we employ iterative in vitro selection and chemical structure probing to identify sequence and structural motif(s) critical for RNA-SMN interactions. Our results reveal that motifs that drive RNA-SMN interactions are diverse and suggest that tight RNA-SMN interaction requires presence of multiple contact sites on the RNA molecule. We performed UV crosslinking and immunoprecipitation coupled with high-throughput sequencing (HITS-CLIP) to identify cellular RNA targets of SMN in neuronal SH-SY5Y cells. Results of HITS-CLIP identified a wide variety of targets, including mRNAs coding for ribosome biogenesis and cytoskeleton dynamics. We show critical determinants of ANXA2 mRNA for a direct SMN interaction in vitro. Our data confirms the ability of SMN to discriminate among close RNA sequences, and represent the first validation of a direct interaction of SMN with a cellular RNA target. Our findings suggest direct RNA-SMN interaction as a novel mechanism to initiate the cascade of events leadi...Continue Reading

Associated Datasets

Feb 9, 2018
Aug 1, 2018

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Citations

Sep 23, 2020·Open Biology·Benita Turner-BridgerJean-Michel Cioni
Feb 6, 2020·Frontiers in Molecular Biosciences·Maximilian Paul Thelen, Min Jeong Kye
Aug 6, 2020·Journal of Personalized Medicine·Piera SmeriglioMaria Grazia Biferi
Dec 8, 2020·Neuroscience Insights·Ravindra N SinghNatalia N Singh
Aug 28, 2021·International Journal of Molecular Sciences·Eric William OttesenRavindra Narayan Singh

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Datasets Mentioned

BETA
GSE110411
SRP132513

Methods Mentioned

BETA
pulldown
SELEX
immunoprecipitation
CLIP
HITS-CLIP
PCR
scraping
RNA-Seq
electrophoretic mobility shift assay
RIP-Chip

Software Mentioned

Fastx
HITS
WebGESTALT
MEME
Tophat
CLIP
SMN
SHAPE
IMPACT
Cutadapt

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