5S ribosomal RNA
|5S ribosomal RNA|
|Predicted secondary structure and sequence conservation of 5S ribosomal RNA|
|RNA type||Gene; rRNA|
|Domain(s)||Eukaryota; Bacteria; Archaea|
The 5S ribosomal RNA (5S rRNA) is a small ribosomal RNA molecule. It makes an important contribution to both the structure and function of the large ribosomal subunit, which in turn, is a major component of the fully functional ribosome. 5S rRNA has been found to be present in the cytosolic ribosomes from all domains of life (bacteria, archaea, and eukaryotes), but is not found in the mitochondrial ribosomes of fungi and animals. The naming of the 5S rRNA follows the standard convention for ribosomal RNA molecules, where the Svedberg unit (S) is used as a measure of the molecule’s sedimentation velocity in an ultracentrifuge.
The 5S rRNA is a relatively small RNA of 120 nucleotides in length and a mass of approximately 40kDa. The secondary structure has been determined and is known to consist of five helices, four loops, and one hinge which forms a Y structure. In the eukaryotic genome the 5S rDNA genes cluster in tandem repeats. The number of these genes is variable from species to species.
The five helices are identified as I-V and the four loops plus one hinge, are identified as A-E. Two of the four loops (C and D) are hairpin loops, and loop B and E are internal loops. Loop A forms the hinge structure.
Helix III has two adenosines that are highly conserved. Phylogenetic studies show that helices I and III are likely ancestral in their structure. Helix V can from a hairpin structure that is thought to interact with TFIIIA.
Eukaryotic 5S rRNA is synthesized by RNA polymerase III, whereas most other eukaroytic rRNAs are cleaved from a 45S precursor transcribed by RNA polymerase I. In Xenopus oocytes, it has been shown that fingers 4-7 of the nine-zinc finger transcription factor TFIIIA can bind to the central region of 5S RNA. Binding between 5S rRNA and TFIIIA serves to both repress further transcription of the 5S RNA gene and stabilize the 5S RNA transcript until it is required for ribosome assembly.
Mapping of 5S rRNA within the ribosome
Using a variety of molecular techniques, including immuno-electron microscopy, intermolecular chemical cross-linking, and X-ray crystallography, the location of the 5S rRNA within the large ribosomal subunit has been determined to great precision. The large ribosomal subunit, itself is composed of two RNA components, the 5S rRNA and another larger RNA known as 23S rRNA, along with multiple associated proteins. The structure of the large ribosomal subunit in 3-dimensions shows one surface that is relatively smooth and the opposite surface with three projections. These projections are known as the L1 protuberance, the central protuberance, and the L7/L12 stalk. The L1 protuberance and L7/L12 stalk are arranged laterally and surround the central protuberance. When apart of the large ribosomal subunit, the 5S rRNA is located in the central protuberance. In fact, its presence is integral to the formation and structure of the central protuberance. The other major components of the central protuberance include the 23S rRNA and several proteins including L5, L18, L25, and L27.
The exact function of 5S rRNA is not clear yet. But in Escherichia coli cells, a deficiency of 5S rRNA has a detrimental effect on cell fitness with greater magnitude than the effects of deleting other rRNA genes such as 16S and 23S. Escherichia coli cells that have loss of 5S rDNA, 5S rRNA, or 5S rRNA-binding proteins have reduced ability to synthesize protein. In addition, crystallographic studies on ribosomes and their functional complexes show that 5S rRNA-binding proteins and other proteins of the central protuberance of the large ribosomal subparticle could play a role in the binding of tRNA with the ribosome. Also, the topographical and physical proximity between 5S rRNA and 23S rRNA which form two functional centers of the ribosome, peptidyl transferase and GTPase-associating ones, has yielded a hypothesis that 5S rRNA could act as a mediator to coordinate between functional centers of the ribosome. Crystallographic studies on ribosomes and confirm the topography and intermolecular contacts of the 5S rRNA-protein complex, and it is shown that the 5S rRNA-protein complex and other components of the central protuberance of the large ribosomal subparticles may play a role in forming intersubunit bridges and tRNA-binding sites.
5S rRNA in ribosomal assembly
In eukaryotic organisms biogenesis of the ribosome is a complex process that requires the assembly of four rRNAs and over 80 proteins. While the biogenesis of the other RNA components of the 60S and 40S ribosomal subunits starts out in the nucleolus with transcription by RNA polymerase I, the 5S rRNA is unique in that it is transcribed by RNA polymerase III from independent genes located in a different chromosomal locus. Rex1p, Rex2p, and Rex3p are exonucleases that process the 3’ ends of 5S rRNA. Once the RNA components are transcribed the final assembly of the ribosome occurs in the cytoplasm. The ribosomal RNA is first exported from the nucleus to the cytoplasm. It is here that the 60S and 40S subunits join to form the mature 80S ribosome, and the process of translation can begin.
The studies present conflicting findings with regard to the stage at which 5S rRNA is integrated into the ribosome; a recent study suggests that 5S rRNAs are associated in the very early 90S step in the ribosomal assembly, but the earlier work suggested that association occurred much later. The recent data obtained with yeast suggest that 5S rRNA is incorporated into 90S particles as part of a small RNP complex, and particularly, in both yeast and mammalian cells, 5S rRNA is found associated with (a homolog of) ribosomal protein L5 (RPL5) in a ribosome-independent small RNP; it seems at least established that it forms pre-ribosomal particles as a 5S rRNA-RPL5 complex.
Several important proteins which interact with 5S rRNA are listed below.
Interaction of 5S rRNA with the La protein is necessary to prevent the RNA from being degraded by exonucleases in the cell. La protein is found in all eukaryotic organisms and is localized to the nucleus, where it associates with several types of RNAs transcribed by RNA pol III. La protein interacts with these RNAs (including the 5S rRNA) through their 3’ uridylates, aiding stability and folding of the RNA.
Ribosomal protein L5 also associates and stabilizes the 5S rRNA. 5S rRNA is unique among ribosomal RNAs in that it can be found outside of the ribosome as part of a ribonucleoprotein particle (RNP). L5 forms a complex with 5S rRNA that is transported to the nucleus for assembly into the ribosome. L5 is therefore, found both in the nucleus and the cytoplasm of eukaryotic cells. Deficiency in normal L5 prevents transport of 5S rRNA to the nucleus and results in decreased ribosomal assembly.
Other Ribosomal Proteins
In prokaryotes the 5S rRNA binds to the L5, L18 and L25 ribosomal proteins, whereas, in eukaryotes 5S rRNA is only known to bind the L5 ribosomal protein. Also, in T. brucei, the causative agent of African typanosomiasis, 5S rRNA interacts with two closely related RNA-binding proteins, P34 and P37, whose loss results in a lowered level of 5S rRNA.
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- Page for 5S ribosomal RNA at Rfam
- 5S Ribosomal RNA at the US National Library of Medicine Medical Subject Headings (MeSH)
- 5S_rRNA human gene location in the UCSC Genome Browser.