Non-coding RNA

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A non-coding RNA (ncRNA) is any RNA molecule that functions without being translated into a protein. A commonly used synonym is small RNA (sRNA). Less-frequently used synonyms are non-messenger RNA (nmRNA), small non-messenger RNA (snmRNA), or functional RNA (fRNA). The DNA sequence from which a non-coding RNA is transcribed as the end product is often called an RNA gene or non-coding RNA gene (see gene).

The most prominent examples of non-coding RNAs are transfer RNA (tRNA) and ribosomal RNA (rRNA), both of which are involved in the process of translation and gene expression. However, since the late 1990s, many new non-coding RNAs have been found, and thus non-coding RNAs may play a much more significant role than previously thought.

Human mitochondrial genome contains 24 RNA genes: 2 for 23S and 16S rRNR subunits of mitochondrial ribosomes. Nuclear genome contains c.a. 3000 RNA genes (less than 10% of total gene number). To identify RNA genes in sequenced DNA is very difficult. In addition to the RNA genes there are many related pseudogene/gene fragments.

Contents

Types (families) of non-coding RNAs

Transfer RNA

Transfer RNA (tRNA) is RNA that transfers a specific amino acid to a growing polypeptide chain at the ribosomal site of protein biosynthesis during translation.

Ribosomal RNA

Ribosomal RNA (rRNA) is the primary constituent of ribosomes. Ribosomes are the protein-manufacturing organelles of cells and exist in the cytoplasm. rRNA is transcribed from DNA, like all RNA. Ribosomal proteins are transported into the nucleus and assembled together with rRNA before being transported through the nuclear membrane. This type of RNA makes up the vast majority of RNA found in a typical cell. While proteins are also present in the ribosomes, solely rRNA is able to form peptides. Therefore ribosome often is referred to as ribozyme.

There are 2 mitochondrial (23S and 16S) rRNA molecules[1]and 4 types of cytoplasmic rRNA (28S, 5.8S, 5S (large ribosome subunit) and 18S (small subunit)). 28S, 5.8S and 18S rRNAs are encoded by a single transcription unit organized into 5 clusters (each has 30-40 repeats) on the 13,14,15, 21 and 22 chromosomes. 5S occurs in tandem arrays (~200-300 true 5S genes and many dispersed pseudogenes), the largest one on the chromosome 1q41-42.

Cytoplasmic rRNA genes are highly repetitive because of huge demand of ribosomes for protein synthesis ('gene dosage') in the cell.

Untranslated regions of mRNAs

Many non-coding RNAs are structural elements in the untranslated regions (see 5'UTR, 3'UTR) of mRNAs (i.e. cis-regulatory RNAs), for example riboswitches and the SECIS element .

Small nuclear RNA

Small nuclear RNA (snRNA) is a class of small RNA molecules that are found within the nucleus of eukaryotic cells. They are transcribed by RNA polymerase II or RNA polymerase III. They are involved in a variety of important processes such as RNA splicing (removal of introns from hnRNA), regulation of transcription factors (7SK RNA) or RNA polymerase II (B2 RNA), and maintaining the telomeres. They are always associated with specific proteins, and the complexes are referred to as small nuclear ribonucleoproteins (snRNP) or sometimes as snurps.

Small nucleolar RNA

Small nucleolar RNAs (snoRNAs) are a class of small RNA molecules that guide chemical modifications (methylation or pseudouridylation) of ribosomal RNAs (rRNAs) and other RNA genes. These modifications are thought to subtly enhance the function of the mature RNA. They are frequently encoded in the introns of ribosomal proteins and are synthesized by RNA polymerase II, but can also be transcribed as independant (sometimem polycistronic) transcriptional units. snoRNAs are a component in the small nucleolar ribonucleoprotein (snoRNP), which contains snoRNA and proteins. The snoRNA guides the snoRNP complex to the modification site of the target RNA gene via sequences (base pairing) in the snoRNA that hybridize to the target site. The proteins then catalyze modification of the RNA gene.

  1. snoRNA lines up the RNA-modifying enzyme at the correct position by complementary base pairing
  2. 2'-O-methylated ribose causes an invrease in the 3'-endo conformation
  3. Pseudouridine (psi) adds another option for H-bonding.
  4. Heavily methylated RNA is protected from hydrolysis. rRNA acts as a ribozyme by catalyzing its own hydrolysis and splicing.

microRNA

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microRNA (also miRNA) are RNA genes that are the reverse complement of another gene's mRNA transcript and inhibit the expression of the target gene.

gRNAs

gRNAs (for guide RNA) are RNA genes that function in RNA editing. Thus far, RNA editing has been found only in the mitochondria of kinetoplastids, in which mRNAs are edited by inserting or deleting stretches of uridylates (Us). The gRNA forms part of the editosome and contains sequences that hybridize to matching sequences in the mRNA, to guide the mRNA modifications.

The term "guide RNA" is also sometimes used generically to mean any RNA gene that guides an RNA/protein complex via hybridization of matching sequences.

efference RNA

Efference RNA (eRNA) is derived from intron sequences of genes or from non-coding DNA. The function is assumed to be regulation of translational activity by interference with the transcription apparatus or target proteins of the translated peptide in question, or by providing a concentration-based measure of protein expression, basically introducing a fine-tuned analog element in gene regulation as opposed to the digital on-or-off regulation by promoters. Research into the role of eRNAs is in its infancy.

Signal recognition particle RNA

The signal recognition particle (SRP) is an RNA-protein complex present in the cytoplasm of cells that binds to the mRNA of proteins that are destined for secretion from the cell. The RNA component of the SRP in eukaryotes is called 4.5S RNA.

pRNA

At least one species of DNA-containing phages, phi-29, uses a complex of six identical short RNA sequences as mechanical components (utilizing ATP for energy) of its DNA packaging machinery. How common this phenomenon is has yet to be determined.

tmRNA

tmRNA has a complex structure with tRNA-like and mRNA-like regions. It has currently only been found in bacteria, but is ubiquitous in all bacteria. tmRNA recognizes ribosomes that have trouble translating or reading an mRNA and stall, leaving an unfinished protein that may be detrimental to the cell. tmRNA acts like a tRNA first, and then an mRNA that encodes a peptide tag. The ribosome translates this mRNA region of tmRNA and attaches the encoded peptide tag to the C-terminus of the unfinished protein. This attached tag targets the protein for destruction or proteolysis. How tmRNA works

External

  • The Rfam Database A curated list of hundreds of families of related ncRNAs. Each family includes a multiple alignment of known members, and predicted homologs in a large genome database. The definition of "family" is a pragmatic one, the goal being to lead to high-quality annotations. Thus, some families are quite broad (e.g. all tRNAs are in one family, as of 2004), while some families are quite narrow (e.g. there are many microRNA families, one for each type).
  • Non-coding RNA database
  • BRaliBase Provides benchmarks and links to a variety of ncRNA analysis for structure prediction, sequence alignment and homology search.
  • miRacle Provides target search for microRNAs and other small non-coding RNAs based on an algorithm which incorporates RNA secondary structure.


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