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⇱ Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs | Nature Reviews Molecular Cell Biology

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Key Points

  • We now understand that genomes in all three domains of life produce functional RNAs that do not encode proteins (non-coding (nc)RNAs), but do exert important influences on diverse cellular processes.

  • Most ncRNAs function with essential partner proteins (that is, as non-coding ribonucleoproteins; ncRNPs) and use cognate antisense elements to interact with target molecules. The small nuclear (sn)RNAs and small nucleolar (sno)RNAs are founding members of the family of ncRNAs that helped to establish these common paradigms.

  • Recent studies of the snRNPs and snoRNPs have revealed unexpectedly elaborate biogenesis pathways that will probably also be travelled by other ncRNPs.

  • snRNAs and snoRNAs can be transcribed from independent promoters (similar to mRNAs) or can be encoded within intronic sequences.

  • RNA function can require multiple partner proteins with roles that might include modulating RNA structure or securing an enzyme, as well as catalysing the reaction.

  • Assembling a functional complex seems to involve a series of non-functional intermediate states that are matured by a series of cellular factors along a defined physical pathway in the cell. These transport and assembly steps might serve as control points for the regulation of the activity of a given ncRNP.

Abstract

Recent advances have fuelled rapid growth in our appreciation of the tremendous number, diversity and biological importance of non-coding (nc)RNAs. Because ncRNAs typically function as ribonucleoprotein (RNP) complexes and not as naked RNAs, understanding their biogenesis is crucial to comprehending their regulation and function. The small nuclear and small nucleolar RNPs are two well studied classes of ncRNPs with elaborate assembly and trafficking pathways that provide paradigms for understanding the biogenesis of other ncRNPs.

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Figure 1: Anatomical features of Sm- and Lsm-class small nuclear RNAs.
The alternative text for this image may have been generated using AI.
Figure 2: Biogenesis of Sm-class small nuclear RNPs.
The alternative text for this image may have been generated using AI.
Figure 3: Anatomical features of C/D and H/ACA RNAs.
The alternative text for this image may have been generated using AI.
Figure 4: Coordinated synthesis, assembly and trafficking of C/D and H/ACA RNPs.
The alternative text for this image may have been generated using AI.

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Acknowledgements

We apologize to our colleagues whose work has not been cited or discussed in full, owing to space constraints. We thank current and past members of the Matera and Terns groups who have contributed to the work in our laboratories. M.P.T. and R.M.T. are grateful to C. Glover for continued scientific discourse. This work was supported by National Institutes of Health (National Institute of Neurological Disorders and Stroke and National Institute of General Medical Sciences) and Muscular Dystrophy Association grants to A.G.M. and by grants from the National Institutes of Health (National Institute of General Medical Sciences and National Cancer Institute) and the Nora L. Redman Fund to M.P.T. and R.M.T.

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Authors and Affiliations

  1. Department of Genetics, Case Western Reserve University, Cleveland, 44106-4955, Ohio, USA

    A. Gregory Matera

  2. Departments of Biochemistry & Molecular Biology, and Genetics, University of Georgia, Athens, 30602, Georgia, USA

    Rebecca M. Terns & Michael P. Terns

  3. Rebecca M. Terns & Michael P. Terns

Authors
  1. A. Gregory Matera
  2. Rebecca M. Terns
  3. Michael P. Terns

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Glossary

Non-coding (nc)RNA

A functional RNA molecule that does not code for a protein (that is, it is not an mRNA).

Adaptor protein

Bridges proteins that link specific cargoes to their cognate transport receptors.

Export/import receptor

Collectively called karyopherins, these proteins facilitate transport across nuclear pores. Import factors are called importins and export factors are called exportins. Receptors primarily mediate interactions with nuclear pores but can also bind cargo directly.

Cajal bodies

Intranuclear structures that function as ribonucleoprotein-assembly, trafficking and remodelling centres.

Perichromatin fibril

(PF). A fine structure, which is visible only under the electron microscope, that is located adjacent to transcriptionally active chromatin and is thought to be a site of active pre-mRNA processing.

Interchromatin granule cluster

(IGC).Corresponds to a nuclear domain visible as a speckle under the light microscope. IGCs function as storage sites for splicing factors that can be recruited to perichromatin fibrils.

Peptidyl transferase centre

Catalytic centre of the ribosome that forms peptide bonds during protein translation.

mRNA-decoding centre

Region of the ribosome involved in the selection of transfer RNAs that correspond to mRNA codons during protein translation.

Kink-turn (k-turn) motif

A common RNA structural motif that is bound by a family of related proteins, including L7Ae, resulting in a sharp bend (or kink) in the RNA helix.

TRAMP complex

A nuclear polyadenylation complex consisting of Trf4 (a poly(A) polymerase), Air2 (a zinc-knuckle protein) and Mtr4 (an RNA helicase). TRAMP functions together with the exosome as a quality-control mechanism to stimulate the degradation of various aberrant target RNAs.

Exosome

A complex of 3β€²β†’5β€² exonucleases that has important roles in RNA processing and turnover.

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Matera, A., Terns, R. & Terns, M. Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs. Nat Rev Mol Cell Biol 8, 209–220 (2007). https://doi.org/10.1038/nrm2124

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