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RNA regulation: a new genetics?

Abstract

Do non-coding RNAs that are derived from the introns and exons of protein-coding and non-protein-coding genes represent a fundamental advance in the genetic operating system of higher organisms? Recent evidence from comparative genomics and molecular genetics indicates that this might be the case. If so, there will be profound consequences for our understanding of the genetics of these organisms, and in particular how the trajectories of differentiation and development and the differences among individuals and species are genomically programmed. But how might this hypothesis be tested?

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Figure 1: The ratio of non-coding to protein-coding DNA rises as a function of developmental complexity.
Figure 2: Double-logarithmic plot of the number of genes that encode regulatory proteins (R) against the total number of genes (G) for bacteria (circles) and archaea (triangles).
Figure 3: A simplified biological history of the Earth.

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Acknowledgements

I thank the members of my research group, collaborators and colleagues for stimulating discussions and for their input into different aspects of this work.

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DATABASES

LocusLink

CFTR

IGF2

lin-4

let-7

SIM2

OMIM

autism

B-cell lymphoma

cartilage-hair hypoplasia

DiGeorge syndrome

lung cancer

prostate cancer

schizophrenia

spinocerebellar ataxia type 8

FURTHER INFORMATION

University of Queensland Institute for Molecular Bioscience

Glossary

EFFERENCE RNA SIGNALS

Regulatory RNA signals that are produced in parallel with the primary gene product that allow forward control and coordination of networks of gene activity.

GENE ONTOLOGY

A hierarchical organization of concepts (ontology) with three organizing principles: molecular function, the tasks done by individual gene products; biological process that are accomplished by ordered assemblies of molecular functions; and cellular components, subcellular structures, locations and macromolecular complexes.

IMPRINTED LOCI

Loci at which the expression of an allele is different depending on whether it is inherited from the mother or the father.

SPLICEOSOME

A ribonucleoprotein complex that is involved in splicing nuclear pre-mRNA. It consists of 5 small nuclear ribonucleoproteins (snRNPs) and more than 50 non-snRNPs, which recognize and assemble on exon–intron boundaries to catalyse the excision of introns from the pre-mRNA.

SUFFIX ARRAYS

An array of all terminal substrings of a sequence string in lexicographical order, which allows a binary search.

SUFFIX TREES

A compact representation of a tree that corresponds to the suffixes of a given string in which all nodes with one child are merged with their parents in a branching structure.

TRANSINDUCTION

The induction of intergenic transcription of the β-globin cluster in non-erythroid cells by the expression of transiently transfected β-globin genes, which is not dependent on protein expression.

TRANSVECTION

Apparent cross-talk between alleles, in which complementation is observed between promoter mutations in one allele and structural mutations in the other, although in many cases the promoter region itself might produce a separate transcript.

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Mattick, J. RNA regulation: a new genetics?. Nat Rev Genet 5, 316–323 (2004). https://doi.org/10.1038/nrg1321

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