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Friday, March 06, 2009

Ribonucleic Acid (RNA)

There was a time in the not-to-distant past when RNA didn't get no respect. Most biochemists worked with proteins or DNA and RNA was relegated to minor status as just an intermediate in the information flow pathway.

We all knew that there were five main types of RNA:
  1. Messenger RNA (mRNA) and its precursors: The primary RNA transcripts are produced by copying the DNA of a protein-encoding gene.1 Subsequent processing steps include addition, removal, and modification of nucleotides as well as splicing events that excise internal segments.2 The mature mRNA is translated to produce a protein whose amino acid sequence is determined by the sequence of the coding region in the gene. The messenger RNA, as the name implies, is the molecule that carries the message from the gene to the protein synthesis machinery. (And from the nucleus to the cytoplam in eukaryotic cells.)

  2. Ribosomal RNA (rRNA): The ribosomes are the most important part of the translation machinery and it has long been known that much of the mass of ribosomes is due to the presence several types of ribosomal RNA. These are noncoding RNAs produced by transcription of ribosomal RNA genes.3 One of the key steps in translation—formation of the peptide bond—is catalyzed by the rRNA component of the ribosome. It is the major catalytic RNA in cells.

  3. Transfer RNA (tRNA): tRNAs are intermediates in protein synthesis. There are many different tRNA molecules in every cell and each one binds a specific amino acid, yielding an aminoacylated-tRNA (aa-tRNA). Each different aminoacylated tRNA interacts with a particular codon in mRNA thus delivering the correct amino acid to to the site of protein synthesis.4

  4. Small RNAs: The small RNAs represent a heterogeneous category of RNAs covering a wide ranges of functions. Some of them have catalytic functions—RNAse P is the classic example.4 Some of them are structural components of ribonucleoprotein complexes (e.g. signal recognition particle).5 Some of them are guide RNAs involved in various processing events. The best known examples of guide RNAs are the small RNAs of the spliceosome complexes that mediate the splicing of mRNA precursors.2 Other small RNAs were known to be involved in the regulation of gene expression.

  5. Genomic RNA: Some viruses, notably retroviruses, have an RNA genome instead of a DNA genome. In addition, the mobility of various transposons is due to an intermediate RNA copy of the transposon sequence (retrotransposons).
This was the state of knowledge 25 years ago. Since then, the study of RNA has made remarkable progress. Our knowledge of all the fundamental processes—transcription, processing, and catalysis—has expanded enormously.

The biggest change is in the area of small RNAs. Today there are several categories of small RNAs—siRNA, microRNA, piRNA—that were only discovered in the past 10-15 years. The functions of these small RNA molecules are still being worked out. There's little doubt that some of them have important biological roles but there's considerable controversy over what percentage might be artifacts of one sort or another.

This month's issue of Cell is devoted to RNA [Cell]. There are important reviews and essays on everything from micro RNAs to spliceosomes and transcriptional scaffolds. This is your chance to catch up on the latest work in the RNA field.

The Centrality of RNA
Phillip A. Sharp

RNA-Based Therapeutics: Ready for Delivery?
Laura Bonetta

MicroRNAs and Cancer: Short RNAs Go a Long Way
Andrea Ventura, Tyler Jacks

Viral RNAs: Lessons from the Enemy
Bryan R. Cullen

Crawling Out of the RNA World
Thomas R. Cech

The Dynamic Landscapes of RNA Architecture
José Almeida Cruz, Eric Westhof

Transcriptional Scaffolds for Heterochromatin Assembly
Hugh P. Cam, Ee Sin Chen, Shiv I.S. Grewal

Regulatory RNAs in Bacteria
Lauren S. Waters, Gisela Storz

Evolution and Functions of Long Noncoding RNAs
Chris P. Ponting, Peter L. Oliver, Wolf Reik

Origins and Mechanisms of miRNAs and siRNAs
Richard W. Carthew, Erik J. Sontheimer

Small RNAs as Guardians of the Genome
Colin D. Malone, Gregory J. Hannon

Origin, Biogenesis, and Activity of Plant MicroRNAs
Olivier Voinnet

Pre-mRNA Processing Reaches Back to Transcription and Ahead to Translation
Melissa J. Moore, Nick J. Proudfoot

The Spliceosome: Design Principles of a Dynamic RNP Machine
Markus C. Wahl, Cindy L. Will, Reinhard Lührmann

mRNA Localization: Gene Expression in the Spatial Dimension
Kelsey C. Martin, Anne Ephrussi

Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets
Nahum Sonenberg, Alan G. Hinnebusch

Fidelity at the Molecular Level: Lessons from Protein Synthesis
Hani S. Zaher, Rachel Green

The Many Pathways of RNA Degradation
Jonathan Houseley, David Tollervey

RNA and Disease
Thomas A. Cooper, Lili Wan, Gideon Dreyfuss

  1. Theme: Transcription.

  2. RNA Splicing: Introns and Exons.

  3. Human Ribosomal RNA genes; Ribosomal RNA Genes in Eukaryotes; Ribosomal RNA Genes in Bacteria; The Composition of Ribosomes

  4. Transfer RNA: Structure; Transfer RNA: Synthesis; Transfer RNA Processing: RNase P.

  5. The Signal hypothesis; Signal Recognition Particle
[Hat Tip: Bayblab - CELL Website Gets Massive RNA Contamination]

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