Ribosomal RNA

Source: Wikipedia, the free encyclopedia.
"RRNA" redirects here. For the company, see Rolls-Royce North America.
rRNAs
rRNAs of various species
Identifiers
Other data
RNA typeGene; rRNA
PDB structuresPDBe

Ribosomal ribonucleic acid (rRNA) is a type of

protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal DNA (rDNA) and then bound to ribosomal proteins to form small and large ribosome subunits. rRNA is the physical and mechanical factor of the ribosome that forces transfer RNA (tRNA) and messenger RNA (mRNA) to process and translate the latter into proteins.[1] Ribosomal RNA is the predominant form of RNA found in most cells; it makes up about 80% of cellular RNA despite never being translated into proteins itself. Ribosomes are composed of approximately 60% rRNA and 40% ribosomal proteins, though this ratio differs between prokaryotes and eukaryotes.[2][3]

Structure

Although the

residues (as opposed to acidic residues) and aromatic residues (i.e. phenylalanine, tyrosine and tryptophan) allowing them to form chemical interactions with their associated RNA regions, such as stacking interactions. Ribosomal proteins can also cross-link to the sugar-phosphate backbone of rRNA with binding sites that consist of basic residues (i.e. lysine and arginine). All ribosomal proteins (including the specific sequences that bind to rRNA) have been identified. These interactions along with the association of the small and large ribosomal subunits result in a functioning ribosome capable of synthesizing proteins.[5]

An example of a fully-assembled small subunit of ribosomal RNA in prokaryotes, specifically Thermus thermophilus. The actual ribosomal RNA (16S) is shown coiled in orange with ribosomal proteins attaching in blue.

Ribosomal RNA organizes into two types of major ribosomal subunit: the large subunit (LSU) and the small subunit (SSU). One of each type come together to form a functioning ribosome. The subunits are at times referred to by their size-sedimentation measurements (a number with an "S" suffix). In prokaryotes, the LSU and SSU are called the 50S and 30S subunits, respectively. In eukaryotes, they are a little larger; the LSU and SSU of eukaryotes are termed the 60S and 40S subunits, respectively.

In the ribosomes of prokaryotes such as bacteria, the SSU contains a single small rRNA molecule (~1500 nucleotides) while the LSU contains one single small rRNA and a single large rRNA molecule (~3000 nucleotides). These are combined with ~50 ribosomal proteins to form ribosomal subunits. There are three types of rRNA found in prokaryotic ribosomes: 23S and 5S rRNA in the LSU and 16S rRNA in the SSU.

In the ribosomes of eukaryotes such as

Eukarya, were reported to possess two supersized ESs in their 23S rRNAs.[9] Likewise, the 5S rRNA contains a 108‐nucleotide insertion in the ribosomes of the halophilic archaeon Halococcus morrhuae.[10][11]

A eukaryotic SSU contains the 18S rRNA subunit, which also contains ESs. SSU ESs are generally smaller than LSU ESs.

SSU and LSU rRNA sequences are widely used for study of evolutionary relationships among organisms, since they are of ancient origin,[12] are found in all known forms of life and are resistant to horizontal gene transfer. rRNA sequences are conserved (unchanged) over time due to their crucial role in the function of the ribosome.[13] Phylogenic information derived from the 16s rRNA is currently used as the main method of delineation between similar prokaryotic species by calculating nucleotide similarity.[14] The canonical tree of life is the lineage of the translation system.

LSU rRNA subtypes have been called ribozymes because ribosomal proteins cannot bind to the catalytic site of the ribosome in this area (specifically the peptidyl transferase center, or PTC).[15]

The SSU rRNA subtypes decode mRNA in its decoding center (DC).[16] Ribosomal proteins cannot enter the DC.

The structure of rRNA is able to drastically change to affect tRNA binding to the ribosome during translation of other mRNAs.[17] In 16S rRNA, this is thought to occur when certain nucleotides in the rRNA appear to alternate base pairing between one nucleotide or another, forming a "switch" that alters the rRNA's conformation. This process is able to affect the structure of the LSU and SSU, suggesting that this conformational switch in the rRNA structure affects the entire ribosome in its ability to match a codon with its anticodon in tRNA selection as well as decode mRNA.[18]

Assembly

Ribosomal RNA's integration and assembly into ribosomes begins with their folding, modification, processing and assembly with ribosomal proteins to form the two ribosomal subunits, the LSU and the SSU. In Prokaryotes, rRNA incorporation occurs in the cytoplasm due to the lack of membrane-bound organelles. In Eukaryotes, however, this process primarily takes place in the nucleolus and is initiated by the synthesis of pre-RNA. This requires the presence of all three RNA polymerases. In fact, the transcription of pre-RNA by RNA polymerase I accounts for about 60% of cell's total cellular RNA transcription.[19] This is followed by the folding of the pre-RNA so that it can be assembled with ribosomal proteins. This folding is catalyzed by endo- and exonucleases, RNA helicases, GTPases and ATPases. The rRNA subsequently undergoes endo- and exonucleolytic processing to remove external and internal transcribed spacers.[20] The pre-RNA then undergoes modifications such as methylation or pseudouridinylation before ribosome assembly factors and ribosomal proteins assemble with the pre-RNA to form pre-ribosomal particles. Upon going under more maturation steps and subsequent exit from the nucleolus into the cytoplasm, these particles combine to form the ribosomes.[20] The basic and aromatic residues found within the primary structure of rRNA allow for favorable stacking interactions and attraction to ribosomal proteins, creating a cross-linking effect between the backbone of rRNA and other components of the ribosomal unit. More detail on the initiation and beginning portion of these processes can be found in the "Biosynthesis" section.

Function

A simplified depiction of a ribosome (with SSU and LSU artificially detached here for visualization purposes) depicting the A and P sites and both the small and large ribosomal subunits operating in conjunction.

Universally conserved secondary structural elements in rRNA among different species show that these sequences are some of the oldest discovered. They serve critical roles in forming the catalytic sites of translation of mRNA. During translation of mRNA, rRNA functions to bind both mRNA and tRNA to facilitate the process of translating mRNA's codon sequence into amino acids. rRNA initiates the catalysis of protein synthesis when tRNA is sandwiched between the SSU and LSU. In the SSU, the mRNA interacts with the anticodons of the tRNA. In the LSU, the amino acid acceptor stem of the tRNA interacts with the LSU rRNA. The ribosome catalyzes ester-amide exchange, transferring the C-terminus of a nascent peptide from a tRNA to the amine of an amino acid. These processes are able to occur due to sites within the ribosome in which these molecules can bind, formed by the rRNA stem-loops. A ribosome has three of these binding sites called the A, P and E sites:

  • In general, the A (aminoacyl) site contains an aminoacyl-tRNA (a tRNA esterified to an amino acid on the 3' end).
  • The P (peptidyl) site contains a
    esterified to the nascent peptide. The free amino (NH2) group of the A site tRNA attacks the ester linkage of P site tRNA, causing transfer of the nascent peptide to the amino acid in the A site. This reaction is takes place in the peptidyl transferase center[15]
  • The E (exit) site contains a tRNA that has been discharged, with a free 3' end (with no amino acid or nascent peptide).

A single mRNA can be translated simultaneously by multiple ribosomes. This is called a polysome.

In prokaryotes, much work has been done to further identify the importance of rRNA in translation of mRNA. For example, it has been found that the A site consists primarily of 16S rRNA. Apart from various protein elements that interact with tRNA at this site, it is hypothesized that if these proteins were removed without altering ribosomal structure, the site would continue to function normally. In the P site, through the observation of crystal structures it has been shown the 3' end of 16s rRNA can fold into the site as if a molecule of mRNA. This results in intermolecular interactions that stabilize the subunits. Similarly, like the A site, the P site primarily contains rRNA with few proteins. The peptidyl transferase center, for example, is formed by nucleotides from the 23S rRNA subunit.[15] In fact, studies have shown that the peptidyl transferase center contains no proteins, and is entirely initiated by the presence of rRNA. Unlike the A and P sites, the E site contains more proteins. Because proteins are not essential for the functioning of the A and P sites, the E site molecular composition shows that it is perhaps evolved later. In primitive ribosomes, it is likely that tRNAs exited from the P site. Additionally, it has been shown that E-site tRNA bind with both the 16S and 23S rRNA subunits.[21]

Subunits and associated ribosomal RNA

Diagram of ribosomal RNA types and how they combine to create the ribosomal subunits.

Both prokaryotic and eukaryotic ribosomes can be broken down into two subunits, one large and one small. The exemplary species used in the table below for their respective rRNAs are the bacterium Escherichia coli (prokaryote) and human (eukaryote). Note that "nt" represents the length of the rRNA type in nucleotides and the "S" (such as in "16S) represents Svedberg units.

Type Size Large subunit (LSU rRNA) Small subunit (SSU rRNA)
prokaryotic 70S
50S (5S : 120 nt, 23S
 : 2906 nt)
30S (16S
 : 1542 nt)
eukaryotic (nuclear) 80S
60S (5S : 121 nt,[22] 5.8S : 156 nt,[23] 28S : 5070 nt[24]
) 		40S (18S : 1869 nt[25])
eukaryotic (mitochondrial) 55S 39S 16S (Mitochondrially encoded 16S rRNA : approx. 1,571 nt) 28S 12S (Mitochondrially encoded 12S rRNA : approx. 955 nt)[26]

S units of the subunits (or the rRNAs) cannot simply be added because they represent measures of sedimentation rate rather than of mass. The sedimentation rate of each subunit is affected by its shape, as well as by its mass. The nt units can be added as these represent the integer number of units in the linear rRNA polymers (for example, the total length of the human rRNA = 7216 nt).

Gene clusters coding for rRNA are commonly called "ribosomal DNA" or rDNA (note that the term seems to imply that ribosomes contain DNA, which is not the case).

In prokaryotes

In prokaryotes a small 30S ribosomal subunit contains the 16S ribosomal RNA. The large 50S ribosomal subunit contains two rRNA species (the 5S and 23S ribosomal RNAs). Therefore it can be deduced that in both bacteria and archaea there is one rRNA gene that codes for all three rRNA types :16S, 23S and 5S.[27]

Bacterial 16S ribosomal RNA, 23S ribosomal RNA, and 5S rRNA genes are typically organized as a co-transcribed operon. As shown by the image in this section, there is an internal transcribed spacer between 16S and 23S rRNA genes.[28] There may be one or more copies of the operon dispersed in the genome (for example, Escherichia coli has seven). Typically in bacteria there are between one and fifteen copies.[27]

Archaea contains either a single rRNA gene operon or up to four copies of the same operon.[27]

The 3' end of the 16S ribosomal RNA (in a ribosome) recognizes a sequence on the 5' end of

Shine-Dalgarno sequence
.

In eukaryotes

Small subunit ribosomal RNA, 5' domain taken from the Rfam database. This example is RF00177, a fragment from an uncultured bacterium.

In contrast,

chromosomes 13 (RNR1), 14 (RNR2), 15 (RNR3), 21 (RNR4) and 22 (RNR5). Diploid humans have 10 clusters of genomic rDNA which in total make up less than 0.5% of the human genome.[29]

It was previously accepted that repeat rDNA sequences were identical and served as redundancies or failsafes to account for natural replication errors and point mutations. However, sequence variation in rDNA (and subsequently rRNA) in humans across multiple chromosomes has been observed, both within and between human individuals. Many of these variations are palindromic sequences and potential errors due to replication.[30] Certain variants are also expressed in a tissue-specific manner in mice.[31]

Mammalian cells have 2 mitochondrial (

12S and 16S) rRNA molecules and 4 types of cytoplasmic rRNA (the 28S, 5.8S, 18S, and 5S subunits). The 28S, 5.8S, and 18S rRNAs are encoded by a single transcription unit (45S) separated by 2 internally transcribed spacers. The first spacer corresponds to the one found in bacteria and archaea, and the other spacer is an insertion into what was the 23S rRNA in prokaryotes.[28] The 45S rDNA is organized into 5 clusters (each has 30–40 repeats) on chromosomes 13, 14, 15, 21, and 22. These are transcribed by RNA polymerase I. The DNA for the 5S subunit occurs in tandem arrays (~200–300 true 5S genes and many dispersed pseudogenes), the largest one on the chromosome 1q41-42. 5S rRNA is transcribed by RNA polymerase III. The 18S rRNA in most eukaryotes is in the small ribosomal subunit, and the large subunit contains three rRNA species (the 5S, 5.8S and 28S
in mammals, 25S in plants, rRNAs).

In flies, the large subunit contains four rRNA species instead of three with a split in the 5.8S rRNA that presents a shorter 5.8S subunit (123 nt) and a 30 nucleotide subunit named the 2S rRNA. Both fragments are separated by an internally transcribed spacer of 28 nucleotides. Since the 2S rRNA is small and highly abundant, its presence can interfere with construction of sRNA libraries and compromise the quantification of other sRNAs. The 2S subunit is retrieved in fruit fly and dark-winged fungus gnat species but absent from mosquitoes.[32]

The tertiary structure of the small subunit ribosomal RNA (SSU rRNA) has been resolved by X-ray crystallography.[33] The secondary structure of SSU rRNA contains 4 distinct domains—the 5', central, 3' major and 3' minor domains. A model of the secondary structure for the 5' domain (500-800 nucleotides) is shown.

Biosynthesis

Main article: Ribosome biogenesis

In eukaryotes

As the building-blocks for the

tRNA and mRNA.[40] Some studies have found that extensive methylation of various rRNA types is also necessary during this time to maintain ribosome stability.[41][42]

The genes for 5S rRNA are located inside the nucleolus and are transcribed into pre-5S rRNA by RNA polymerase III.[43] The pre-5S rRNA enters the nucleolus for processing and assembly with 28S and 5.8S rRNA to form the LSU. 18S rRNA forms the SSUs by combining with numerous ribosomal proteins. Once both subunits are assembled, they are individually exported into the cytoplasm to form the 80S unit and begin initiation of translation of mRNA.[44][45]

Ribosomal RNA is non-coding and is never translated into proteins of any kind: rRNA is only transcribed from rDNA and then matured for use as a structural building block for ribosomes. Transcribed rRNA is bound to ribosomal proteins to form the subunits of ribosomes and acts as the physical structure that pushes mRNA and tRNA through the ribosome to process and translate them.[1]

Eukaryotic regulation

Synthesis of rRNA is up-regulated and down-regulated to maintain homeostasis by a variety of processes and interactions:

  • The
    AKT indirectly promotes synthesis of rRNA as RNA polymerase I is AKT-dependent.[46]
  • Certain angiogenic ribonucleases, such as angiogenin (ANG), can translocate and accumulate in the nucleolus. When the concentration of ANG becomes too high, some studies have found that ANG can bind to the promoter region of rDNA and unnecessarily increase rRNA transcription. This can be damaging to the nucleolus and can even lead to unchecked transcription and cancer.[47]
  • During times of cellular glucose restriction,
    transcription initiation.[48]
  • Impairment or removal of more than one pseudouridine or 29-O-methylation regions from the ribosome decoding center significantly reduces rate of rRNA transcription by reducing the rate of incorporation of new amino acids.[49]
  • Formation of heterochromatin is essential to silencing rRNA transcription, without which ribosomal RNA is synthesized unchecked and greatly decreases the lifespan of the organism.[50]

In prokaryotes

Similar to

metabolic activity dependent on its needs and available resources.[51][52][53]

In

tRNA sequences along with transcribed spacers. The RNA processing then begins before the transcription is complete. During processing reactions, the rRNAs and tRNAs are released as separate molecules.[54]

Prokaryotic regulation

Because of the vital role rRNA plays in the cell physiology of prokaryotes, there is much overlap in rRNA regulation mechanisms. At the transcriptional level, there are both positive and negative effectors of rRNA transcription that facilitate a cell's maintenance of homeostasis:

Degradation

Ribosomal RNA is quite stable in comparison to other common types of RNA and persists for longer periods of time in a healthy cellular environment. Once assembled into functional units, ribosomal RNA within ribosomes are stable in the stationary phase of the cell life cycle for many hours.[55] Degradation can be triggered via "stalling" of a ribosome, a state that occurs when the ribosome recognizes faulty mRNA or encounters other processing difficulties that causes translation by the ribosome to cease. Once a ribosome stalls, a specialized pathway on the ribosome is initiated to target the entire complex for disassembly.[56]

In eukaryotes

As with any protein or RNA, rRNA production is prone to errors resulting in the production of non-functional rRNA. To correct this, the cell allows for degradation of rRNA through the non-functional rRNA decay (NRD) pathway.[57] Much of the research in this topic was conducted on eukaryotic cells, specifically Saccharomyces cerevisiae yeast. Currently, only a basic understanding of how cells are able to target functionally defective ribosomes for ubiquination and degradation in eukaryotes is available.[58]

  • The NRD pathway for the 40S subunit may be independent or separate from the NRD pathway for the 60S subunit. It has been observed that certain genes were able to affect degradation of certain pre-RNAs, but not others.[59]
  • Numerous proteins are involved in the NRD pathway, such as Mms1p and Rtt101p, which are believed to complex together to target ribosomes for degradation. Mms1p and Rtt101p are found to bind together and Rtt101p is believed to recruit a ubiquitin E3 ligase complex, allowing for the non-functional ribosomes to be ubiquinated before being degraded.[60]
    • Prokaryotes lack a homolog for Mms1, so it is unclear how prokaryotes are able to degrade non-functional rRNAs.
  • The growth rate of
    eukaryotic cells
    did not seem to be significantly affected by the accumulation of non-functional rRNAs.

In prokaryotes

Although there is far less research available on ribosomal RNA degradation in prokaryotes in comparison to eukaryotes, there has still been interest on whether bacteria follow a similar degradation scheme in comparison to the NRD in eukaryotes. Much of the research done for prokaryotes has been conducted on Escherichia coli. Many differences were found between eukaryotic and prokaryotic rRNA degradation, leading researchers to believe that the two degrade using different pathways.[61]

Sequence conservation and stability

Due to the prevalent and unwavering nature of rRNA across all

gene transfer, mutation, and alteration without destruction of the organism has become a popular field of interest. Ribosomal RNA genes have been found to be tolerant to modification and incursion. When rRNA sequencing is altered, cells have been found to become compromised and quickly cease normal function.[62] These key traits of rRNA have become especially important for gene database projects (comprehensive online resources such as SILVA[63] or SINA[64]) where alignment of ribosomal RNA sequences from across the different biologic domains greatly eases "taxonomic assignment, phylogenetic analysis and the investigation of microbial diversity."[63]

Examples of resilience:

Significance

This diagram depicts how rRNA sequencing in prokaryotes can ultimately be used to produce pharmaceuticals to combat disease caused by the very microbes the rRNA was originally obtained from.

Ribosomal RNA characteristics are important in evolution, thus taxonomy and medicine.

Human genes

See also

References

  1. ^
    ISBN 9783110810578
    .
  2. ^ Davidson, Michael W. (13 November 2015). "Molecular Expressions Cell Biology: Ribosomes". Molecular Expressions. National High Magnetic Field Laboratory. Retrieved 2024-03-29.
  3. ^ "Ribosome | Definition, Function, Formation, Role, Importance, & Facts | Britannica". Encyclopedia Britannica. 2024-03-08. Retrieved 2024-03-29.
  4. ^ Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James (2000). "The Three Roles of RNA in Protein Synthesis". Molecular Cell Biology. 4th Edition.
  5. PMID 7556101
    .
  6. PMID 16246728
    .
  7. PMID 12564956
    .
  8. PMID 25346433
    .
  9. PMID 32785681
    .
  10. S2CID 4341755
    .
  11. PMID 32865340
    .
  12. PMID 270744
    .
  13. PMID 17452365
    .
  14. PMID 17911292
    .
  15. ^
    PMID 34756086
    .
  16. PMID 26779416
    .
  17. PMID 9271564
    .
  18. PMID 10562562
    .
  19. PMID 24190922
    .
  20. ^
    S2CID 58650367
    .
  21. S2CID 4324362
    .
  22. ^ "Homo sapiens RNA, 5S ribosomal". National Center for Biotechnology Information (NCBI). 2020-09-03. Retrieved 2024-01-06.
  23. ^ "Homo sapiens 5.8S ribosomal RNA". National Center for Biotechnology Information (NCBI). 2017-02-10.
  24. ^ "Homo sapiens 28S ribosomal RNA". National Center for Biotechnology Information (NCBI). 2017-02-04.
  25. ^ "Homo sapiens 18S ribosomal RNA". National Center for Biotechnology Information (NCBI). 2017-02-04.
  26. PMID 25797916
    .
  27. ^
    PMID 25414355
    .
  28. ^
    S2CID 2637106
    .
  29. S2CID 6162867
    .
  30. PMID 29788454
    .
  31. PMID 29503865
    .
  32. S2CID 46570307
    .
  33. S2CID 39505192
    .
  34. ^ "Ribosomal RNA | genetics". Encyclopedia Britannica. Retrieved 2019-10-02.
  35. PMID 21045541
    .
  36. S2CID 205235881
    .
  37. S2CID 205236187
    .
  38. PMID 21349877
    .
  39. PMID 21714483
    .
  40. PMID 27911188
    .
  41. PMID 25125595
    .
  42. PMID 19356719
    .
  43. PMID 14631041
    .
  44. ^ "rRNA synthesis and processing".
  45. ^
    PMID 17468501
    .
  46. S2CID 20979505
    .
  47. PMID 21743803
    .
  48. PMID 19815529
    .
  49. PMID 19628622
    .
  50. PMID 22291607
    .
  51. ^
    PMID 9405339
    .
  52. PMID 26717514
    .
  53. PMID 27898392
    .
  54. ISBN 978-0534124083
    .
  55. PMID 21460796
    .
  56. PMID 26733220
    .
  57. PMID 19390089
    .
  58. ISSN 0892-6638.{{cite journal}}: CS1 maint: DOI inactive as of January 2024 (link
    )
  59. PMID 17188037
    .
  60. S2CID 33099674
    .
  61. PMID 25578614
    .
  62. S2CID 206522454
    .
  63. ^
    PMID 23193283
    .
  64. PMID 22556368
    .
  65. ^
    PMID 20338515
    .
  66. PMID 20060060
    .
  67. PMID 22544737
    .
  68. PMID 20214780
    .
  69. PMID 12520046
    .
  70. PMID 17947321
    .
  71. S2CID 36002898
  72. S2CID 23728518
    .
  73. PMID 24346612
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Ribosomal_RNA&oldid=1216229875"