Human RNA

The image shows red human RNA viroplasms. Credit: ICGEB.

Ribonucleic acid (RNA), specifically human RNA, “is made up of a long chain of components called nucleotides. Each nucleotide consists of a nucleobase, a ribose sugar, and a phosphate group. The sequence of nucleotides allows RNA to encode genetic information. All cellular organisms use messenger RNA (mRNA) to carry the genetic information that directs the synthesis of proteins.”[1]

Ribonucleic acids

"[A]t least three-quarters of the [human] genome is involved in making RNA".[2]

Structure

This diagram shows a portion of the chemical structure of RNA containing guanine. Credit: Narayanese.

“Each nucleotide in RNA contains a ribose sugar, with carbons numbered 1' through 5'. A base is attached to the 1' position, in general, adenine (A), cytosine (C), guanine (G), or uracil (U). Adenine and guanine are purines, cytosine, and uracil are pyrimidines. A phosphate group is attached to the 3' position of one ribose and the 5' position of the next. The phosphate groups have a negative charge each at physiological pH, making RNA a charged molecule (polyanion).”[1]

Introns

"[S]ome introns themselves encode specific proteins or can be further processed after splicing to generate noncoding RNA molecules.[3] Alternative splicing is widely used to generate multiple proteins from a single gene. Furthermore, some introns represent mobile genetic elements and may be regarded as examples of selfish DNA.[4]"[5]

Messenger RNAs

“Messenger RNA (mRNA) is the RNA that carries information from DNA to the ribosome, the sites of protein synthesis (translation) in the cell. The coding sequence of the mRNA determines the amino acid sequence in the protein that is produced.[6] Many RNAs do not code for protein however (about 97% of the transcriptional output is non-protein-coding in eukaryotes[7][8][9][10]).”[1]

Non-coding RNAs

The various “non-coding RNAs ("ncRNA") can be encoded by their own genes (RNA genes), but can also derive from mRNA introns.[11]”[1]

"[S]ome DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression.[12]"[13]

Transfer RNAs

“Transfer RNA (tRNA) is a small RNA chain of about 80 nucleotides that transfers a specific amino acid to a growing polypeptide chain at the ribosomal site of protein synthesis during translation. It has sites for amino acid attachment and an anticodon region for codon recognition that binds to a specific sequence on the messenger RNA chain through hydrogen bonding.[11]”[1]

Ribosomal RNA

“Ribosomal RNA (rRNA) is the catalytic component of the ribosomes. Eukaryotic ribosomes contain four different rRNA molecules: 18S, 5.8S, 28S and 5S rRNA. Three of the rRNA molecules are synthesized in the nucleolus, and one is synthesized elsewhere. In the cytoplasm, ribosomal RNA and protein combine to form a nucleoprotein called a ribosome. The ribosome binds mRNA and carries out protein synthesis. Several ribosomes may be attached to a single mRNA at any time.[6] Nearly all the RNA found in a typical eukaryotic cell is rRNA.”[1]

MicroRNAs

“MicroRNAs (miRNA; 21-22 [nucleotide] nt) are found in eukaryotes and act through RNA interference (RNAi), where an effector complex of miRNA and enzymes can cleave complementary mRNA, block the mRNA from being translated, or accelerate its degradation.[14][15]”[1]

Small interfering RNAs

“[T]here are also endogenous sources of [small interfering RNAs] siRNAs.[16][17] siRNAs act through RNA interference in a fashion similar to miRNAs. Some miRNAs and siRNAs can cause genes they target to be methylated, thereby decreasing or increasing transcription of those genes.[18][19][20]”[1]

Piwi-interacting RNAs

“Animals have Piwi-interacting RNAs (piRNA; 29-30 nt) that are active in germline cells and are thought to be a defense against transposons and play a role in gametogenesis.[21][22]”[1]

Small nuclear RNAs

"Small nuclear ribonucleic acid (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 and 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) often pronounced "snurps". These elements are rich in uridine content."[23]

Small nucleolar RNAs

"In eukaryotes, dozens of posttranscriptional modifications are directed to specific nucleotides in ribosomal RNAs (rRNAs) by small nucleolar RNAs (snoRNAs)."[24]

"Ribosome biogenesis in Eukarya occurs in the nucleolus. Several nucleolar proteins (NOPs), including fibrillarin, Nop56, and Nop58, and dozens of snoRNAs are involved in this process (1). The snoRNAs fall into two major classes: C/D box and H/ACA box RNAs. The C/D box snoRNAs are efficiently precipitated with antibodies against fibrillarin. Most C/D box snoRNAs target specific ribose methylations within rRNA, whereas most H/ACA box RNAs target specific conversions of uridine to pseudouridine within rRNA (2)."[24]

"The general mechanism of C/D box snoRNA-targeted ribose methylation[: ] Each snoRNA contains a 9- to 21-nucleotide (nt)–long sequence, located 5' to the D or D' box motif, that is complementary to an rRNA target sequence. Methylation is directed to the rRNA nucleotide that participates in the base pair 5 nt upstream from the start of the D or D' box. It is likely that most, if not all, eukaryotic rRNA ribose methylations are guided by snoRNAs."[24]

Research

Hypothesis:

  1. Human RNA probably makes up less than 50 % of the RNA produced by the human genome.

Control groups

This is an image of a Lewis rat. Credit: Charles River Laboratories.

The findings demonstrate a statistically systematic change from the status quo or the control group.

“In the design of experiments, treatments [or special properties or characteristics] are applied to [or observed in] experimental units in the treatment group(s).[25] In comparative experiments, members of the complementary group, the control group, receive either no treatment or a standard treatment.[26]"[27]

Proof of concept

Def. a “short and/or incomplete realization of a certain method or idea to demonstrate its feasibility"[28] is called a proof of concept.

Def. evidence that demonstrates that a concept is possible is called proof of concept.

The proof-of-concept structure consists of

  1. background,
  2. procedures,
  3. findings, and
  4. interpretation.[29]

See also

References

  1. 1 2 3 4 5 6 7 8 9 "RNA, In: Wikipedia". San Francisco, California: Wikimedia Foundation, Inc. September 7, 2012. Retrieved 2012-09-07.
  2. ↑ Associated Press (September 5 2012). "Far from being mostly junk, human DNA is ‘a jungle’ of complex activity, huge project shows". The Washington Post. Retrieved 2012-09-06.
  3. ↑ Rearick D, Prakash A, McSweeny A, Shepard SS, Fedorova L, Fedorov A (March 2011). "Critical association of ncRNA with introns". Nucleic Acids Res. 39 (6): 2357–66. doi:10.1093/nar/gkq1080. PMID 21071396. PMC 3064772. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3064772/.
  4. ↑ Lambowitz AM, Belfort M (1993). "Introns as mobile genetic elements". Annu. Rev. Biochem. 62: 587–622. doi:10.1146/annurev.bi.62.070193.003103. PMID 8352597.
  5. ↑ "Intron, In: Wikipedia". San Francisco, California: Wikimedia Foundation, Inc. December 10, 2012. Retrieved 2012-12-13.
  6. 1 2 Cooper GC, Hausman RE (2004). The Cell: A Molecular Approach (3rd ed.). Sinauer. pp. 261–76, 297, 339–44. ISBN 0-87893-214-3. OCLC 52121379 52359301 56050609 174924833 52121379 52359301 56050609.
  7. ↑ Mattick JS, Gagen MJ (1 September 2001). "The evolution of controlled multitasked gene networks: the role of introns and other noncoding RNAs in the development of complex organisms". Mol. Biol. Evol. 18 (9): 1611–30. doi:10.1093/oxfordjournals.molbev.a003951. PMID 11504843. http://mbe.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11504843.
  8. ↑ JS Mattick (2001). "Noncoding RNAs: the architects of eukaryotic complexity". EMBO Reports 2 (11): 986–91. doi:10.1093/embo-reports/kve230. PMID 11713189. PMC 1084129. http://emboreports.npgjournals.com/cgi/content/full/2/11/986.
  9. ↑ Mattick JS (October 2003). "Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms". BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology 25 (10): 930–9. doi:10.1002/bies.10332. PMID 14505360. http://www.imb-jena.de/jcb/journal_club/mattick2003.pdf.
  10. ↑ Mattick JS (October 2004). "The hidden genetic program of complex organisms". Scientific American 291 (4): 60–7. doi:10.1038/scientificamerican1004-60. PMID 15487671. http://www.sciam.com/article.cfm?articleID=00045BB6-5D49-1150-902F83414B7F4945.
  11. 1 2 Wirta W (2006). Mining the transcriptome – methods and applications. Stockholm: School of Biotechnology, Royal Institute of Technology. ISBN 91-7178-436-5. OCLC 185406288. http://kth.diva-portal.org/smash/get/diva2:10803/FULLTEXT01.
  12. ↑ The ENCODE Project Consortium (2007). "Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project". Nature 447 (7146): 799–816. doi:10.1038/nature05874. PMID 17571346. PMC 2212820. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2212820/.
  13. ↑ "DNA, In: Wikipedia". San Francisco, California: Wikimedia Foundation, Inc. December 4, 2012. Retrieved 2012-12-13.
  14. ↑ Wu L, Belasco JG (January 2008). "Let me count the ways: mechanisms of gene regulation by miRNAs and siRNAs". Mol. Cell 29 (1): 1–7. doi:10.1016/j.molcel.2007.12.010. PMID 18206964.
  15. ↑ Matzke MA, Matzke AJM (2004). "Planting the seeds of a new paradigm". PLoS Biology 2 (5): e133. doi:10.1371/journal.pbio.0020133. PMID 15138502. PMC 406394. //www.ncbi.nlm.nih.gov/pmc/articles/PMC406394/.
  16. ↑ Vazquez F, Vaucheret H, Rajagopalan R, Lepers C, Gasciolli V, Mallory AC, Hilbert J, Bartel DP, Crété P (2004). "Endogenous trans-acting siRNAs regulate the accumulation of Arabidopsis mRNAs". Molecular Cell 16 (1): 69–79. doi:10.1016/j.molcel.2004.09.028. PMID 15469823.
  17. ↑ Watanabe T, Totoki Y, Toyoda A, et al. (May 2008). "Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes". Nature 453 (7194): 539–43. doi:10.1038/nature06908. PMID 18404146.
  18. ↑ Sontheimer EJ, Carthew RW (July 2005). "Silence from within: endogenous siRNAs and miRNAs". Cell 122 (1): 9–12. doi:10.1016/j.cell.2005.06.030. PMID 16009127.
  19. ↑ Doran G (2007). "RNAi – Is one suffix sufficient?". Journal of RNAi and Gene Silencing 3 (1): 217–19. http://libpubmedia.co.uk/RNAiJ-Issues/Issue-5/Doran.htm.
  20. ↑ Pushparaj PN, Aarthi JJ, Kumar SD, Manikandan J (2008). "RNAi and RNAa — The Yin and Yang of RNAome". Bioinformation 2 (6): 235–7. doi:10.6026/97320630002235. PMID 18317570. PMC 2258431. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2258431/.
  21. ↑ Horwich MD, Li C Matranga C, Vagin V, Farley G, Wang P, Zamore PD (2007). "The Drosophila RNA methyltransferase, DmHen1, modifies germline piRNAs and single-stranded siRNAs in RISC". Current Biology 17 (14): 1265–72. doi:10.1016/j.cub.2007.06.030. PMID 17604629.
  22. ↑ Girard A, Sachidanandam R, Hannon GJ, Carmell MA (2006). "A germline-specific class of small RNAs binds mammalian Piwi proteins". Nature 442 (7099): 199–202. doi:10.1038/nature04917. PMID 16751776.
  23. ↑ "Small nuclear RNA, In: Wikipedia". San Francisco, California: Wikimedia Foundation, Inc. April 20, 2012. Retrieved 2012-09-07.
  24. 1 2 3 Arina D. Omer, Todd M. Lowe, Anthony G. Russell, Holger Ebhardt, Sean R. Eddy, Patrick P. Dennis (21 April 2000). "Homologs of Small Nucleolar RNAs in Archaea". Science 288 (5465): 517-22. doi:10.1126/science.288.5465.517. ftp://selab.janelia.org/pub/publications/Omer00/Omer00-reprint.pdf. Retrieved 2015-06-27.
  25. ↑ Klaus Hinkelmann, Oscar Kempthorne (2008). Design and Analysis of Experiments, Volume I: Introduction to Experimental Design (2nd ed.). Wiley. ISBN 978-0-471-72756-9. http://books.google.com/?id=T3wWj2kVYZgC&printsec=frontcover.
  26. ↑ R. A. Bailey (2008). Design of comparative experiments. Cambridge University Press. ISBN 978-0-521-68357-9. http://www.cambridge.org/uk/catalogue/catalogue.asp?isbn=9780521683579.
  27. ↑ "Treatment and control groups, In: Wikipedia". San Francisco, California: Wikimedia Foundation, Inc. May 18, 2012. Retrieved 2012-05-31.
  28. ↑ "proof of concept, In: Wiktionary". San Francisco, California: Wikimedia Foundation, Inc. November 10, 2012. Retrieved 2013-01-13.
  29. ↑ Ginger Lehrman and Ian B Hogue, Sarah Palmer, Cheryl Jennings, Celsa A Spina, Ann Wiegand, Alan L Landay, Robert W Coombs, Douglas D Richman, John W Mellors, John M Coffin, Ronald J Bosch, David M Margolis (August 13, 2005). "Depletion of latent HIV-1 infection in vivo: a proof-of-concept study". Lancet 366 (9485): 549-55. doi:10.1016/S0140-6736(05)67098-5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1894952/. Retrieved 2012-05-09.

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