A Transcriptome-wide Atlas of RNP Composition Reveals Diverse Classes of mRNAs and lncRNAs

Summary

Eukaryotic genomes generate a heterogeneous ensemble of mRNAs and long noncoding RNAs (lncRNAs). LncRNAs and mRNAs are both transcribed by Pol II and acquire 5′ caps and poly(A) tails, but only mRNAs are translated into proteins. To address how these classes are distinguished, we identified the transcriptome-wide targets of 13 RNA processing, export, and turnover factors in budding yeast. Comparing the maturation pathways of mRNAs and lncRNAs revealed that transcript fate is largely determined during 3′ end formation. Most lncRNAs are targeted for nuclear RNA surveillance, but a subset with 3′ cleavage and polyadenylation features resembling the mRNA consensus can be exported to the cytoplasm. The Hrp1 and Nab2 proteins act at this decision point, with dual roles in mRNA cleavage/polyadenylation and lncRNA surveillance. Our data also reveal the dynamic and heterogeneous nature of mRNA maturation, and highlight a subset of “lncRNA-like” mRNAs regulated by the nuclear surveillance machinery.

Graphical Abstract

Highlights

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  Transcriptome-wide analysis shows dynamic assembly of ribonucleoprotein particles

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  LncRNA and mRNA subclasses undergo distinct maturation and turnover pathways

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  Transcript fate is determined during 3′ end formation

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  Transcript classes overlap, with many “mRNA-like” lncRNAs and “lncRNA-like” mRNAs

Abstract

A transcriptome-wide analysis shows that different classes of mRNAs and lncRNAs are characterized by distinct 3′ end formation and RNP complexes, explaining how cells distinguish among these otherwise similar RNAs.