Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Regulation of mRNA Levels by Suicidal Introns that Induce Nuclear Decay

ABSTRACT: In eukaryotic cells, inefficient splicing is surprisingly common and leads to degradation of transcripts with retained introns. How pre-mRNAs are committed to nuclear decay is unknown. Here we uncover a mechanism by which intronic transcripts are targeted for nuclear degradation in fission yeast. Surprisingly, sequence elements within âsuicidalâ introns co-transcriptionally recruit the exosome adaptor Mmi1 not only to degrade unspliced precursor, but also to downregulate levels of the resulting mRNA. Under conditions permissive for fast splicing, Mmi1 is no longer recruited and negative expression regulation is relieved. This mechanism negatively regulates levels of the RNA-helicase DDX5/Dbp2 to ensure cell survival in response to stress. We propose that suicidal introns are maintained because they facilitate regulation of gene expression. We identify multiple novel Mmi1 targets including mRNAs, non-coding RNAs, and sn/snoRNAs. We suggest a general role in RNA regulation for Mmi1 beyond degradation of meiotic transcripts. Two biological replicates of CRAC experiments (Control and Mmi1-HTP). Six RNAseq datasets in total: three biological replicates of wt and delta Mmi1 strain.

ORGANISM(S): Schizosaccharomyces pombe

SUBMITTER: Sander Granneman

PROVIDER: E-GEOD-73144 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The green alga Volvox carteri is a model organism for the development of multicellularity. It has a spherical shape with a complete division of labor between around 2000 somatic cells and 16 reproductive cells. When comparing Volvox with its unicellular relative Chlamydomonas rheinhardtii, one striking observation is the similarity in the protein coding genes [1]. Additionally, Baulcombe and colleagues showed that Chlamydomonas contains functional RNAi and miRNA machineries [2]. We deep sequenced small RNAs of the female Volvox strain HK10 in different life stages (asexual reproduction to sexual reproduction), each time dividing the samples into somatic cells and reproductive cells. This allowed for the observation not only of differences in individual life stages, but also for monitoring sRNA content in the two cell types. We show that Volvox expresses miRNAs and that they are 2â??-O-methylated at the 3â?? end. The expression profiles of several miRNAs were validated by Northern blotting showing a differential expression both between cell types and between life stages. Intriguingly, most miRNAs do not seem to be conserved between Volvox and Chlamydomonas, raising the interesting question if this changed miRNome leads to differently targeted mRNAs thus resulting in cell differentiation. Since only little is known about the transcriptome of Volvox, we performed RNASeq in order to analyze potential miRNA targets. In conclusion, most miRNA in Volvox are not conserved in Chlamydomonas although the two species are evolutionary close together. This suggests that dramatic changes in the miRNA expression might be one of the driving forces for the development of multicellularity. 1. Prochnik, S.E., et al., Genomic analysis of organismal complexity in the multicellular green alga Volvox carteri. Science, 2010. 329(5988): p. 223-6. 2. Molnar, A., et al., miRNAs control gene expression in the single-cell alga Chlamydomonas reinhardtii. Nature, 2007. 447(7148): p. 1126-9. Examination of small RNAs of Volvox carteri during different stages of its life cycle

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Regulation of mRNA Levels by Suicidal Introns that Induce Nuclear Decay

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