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SmithRNAs: A Common Feature among Metazoa.

Giovanni Marturano1, Diego Carli2, Claudio Cucini1,3

  • 1Department of Life Sciences, University of Siena, Siena 53100, Italy.

Genome Biology and Evolution
|November 8, 2025
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Summary
This summary is machine-generated.

SmithRNAs, small noncoding RNAs from mitochondrial DNA, are common across Metazoa and regulate nuclear gene expression. Their widespread presence suggests a fundamental biological role beyond specific species.

Keywords:
microRNAsmito-nuclear interactionsmitochondrial genomemitochondrial retrograde responseregulationsmall RNAssncRNAs

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Area of Science:

  • Molecular Biology
  • Genomics
  • Evolutionary Biology

Background:

  • SmithRNAs are novel small noncoding RNAs encoded in mitochondrial genomes.
  • Their function in regulating nuclear transcripts was recently confirmed in the Manila clam.
  • The evolutionary conservation and broader distribution of smithRNAs across Metazoa remained largely unknown.

Purpose of the Study:

  • To investigate the presence and biological features of smithRNAs across a wide range of Metazoan species.
  • To determine if smithRNAs are a conserved feature of Metazoa or unique to specific species.
  • To propose a transcriptional mechanism for smithRNA biogenesis and identify their potential nuclear targets.

Main Methods:

  • Selection of 14 species representing major metazoan lineages.
  • Collection and de novo sequencing/assembly of small RNAseq data, transcriptomes, and genomes.
  • Analysis using the SmithHunter pipeline for smithRNA identification and target prediction.

Main Results:

  • Candidate smithRNAs were identified in all 14 species studied, indicating they are a common feature across Metazoa.
  • SmithRNAs are typically encoded within other genes, preferably on mitochondrial rRNAs and tRNAs.
  • A transcription model suggests smithRNAs are cleaved from primary mitochondrial transcripts; nuclear targets show variability, often related to regulation, mitochondrial function, and reproduction.

Conclusions:

  • SmithRNAs are a conserved feature across Metazoa, not unique to bivalves.
  • A proposed biogenesis mechanism involves post-transcriptional processing of mitochondrial gene transcripts.
  • SmithRNAs likely play diverse regulatory roles, impacting nuclear gene expression, mitochondrial activity, and reproductive processes.