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The human mitochondrial mRNA structurome reveals mechanisms of gene expression

ABSTRACT: The human mitochondrial mRNA structurome reveals mechanisms of gene expression

PROVIDER: PRJNA1033566 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26586100_1.fastq.gz	Fastqsanger.gz
	SRR26586100_2.fastq.gz	Fastqsanger.gz
	SRR26586101_1.fastq.gz	Fastqsanger.gz
	SRR26586101_2.fastq.gz	Fastqsanger.gz
	SRR26586102_1.fastq.gz	Fastqsanger.gz

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The human mitochondrial mRNA structurome reveals mechanisms of gene expression

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Profiling of mRNA localization of nuclear-encoded mitochondrial proteins in zebrafish.

Project description:Current evidence suggests that nuclear-encoded mitochondrial proteins can be locally translated at the mitochondrial surface and co-translationally or post-translationally imported into mitochondria. mRNA localization on the mitochondrial membrane, a prerequisite for localized translation, remains uncharacterized in higher eukaryotic organisms. We employed fractionation-sequencing to profile mitochondria-associated mRNAs in zebrafish larvae. Our transcriptome-wide analysis reveals the localization of mRNAs of only 12% of the nuclear-encoded mitochondrial proteins to the mitochondrial surface, which suggests that post-translational import is the dominant mode of protein import to mitochondria. Additionally, the mRNAs which were localized to the mitochondrial membrane consisted mostly of those encoding proteins involved in mitochondrial dynamics, suggesting their site-specific translation. Finally, we show that the loss of function of the MIA pathway responsible for the post-translational import of a subclass of mitochondrial proteins, triggers mitochondrial localization of mRNAs encoding proteins that are imported to mitochondria via other pathways. Thus, our study suggests that mRNA targeting and localized translation could be relevant in higher eukaryotes to combat stress conditions affecting mitochondrial biogenesis in general.

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In vivo nuclear RNA structurome reveals RNA-structure regulation of mRNA processing in plants.

Project description:BackgroundmRNA processing is critical for gene expression. A challenge in regulating mRNA processing is how to recognize the actual mRNA processing sites, such as splice and polyadenylation sites, when the sequence content is insufficient for this purpose. Previous studies suggested that RNA structure affects mRNA processing. However, the regulatory role of RNA structure in mRNA processing remains unclear.ResultsHere, we perform in vivo selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) chemical profiling on Arabidopsis and generate the in vivo nuclear RNA structure landscape. We find that nuclear mRNAs fold differently from cytosolic mRNAs across translation start and stop sites. Notably, we discover a two-nucleotide single-stranded RNA structure feature upstream of 5' splice sites that is strongly associated with splicing and the selection of alternative 5' splice sites. The regulatory role of this RNA structure feature is further confirmed by experimental validation. Moreover, we find the single-strandedness of branch sites is also associated with 3' splice site recognition. We also identify an RNA structure feature comprising two close-by single-stranded regions that is specifically associated with both polyadenylation and alternative polyadenylation events.ConclusionsWe successfully identify pre-mRNA structure features associated with splicing and polyadenylation at whole-genome scale and validate an RNA structure feature which can regulate splicing. Our study unveils a new RNA structure regulatory mechanism for mRNA processing.

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