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Small RNA (sRNA) are polymeric RNA molecules that are less than 200 nucleotides in length, and are usually non-coding. RNA silencing is often a function of these molecules, with the most common and well-studied example being RNA interference (RNAi), in which microRNA (miRNA) from the organism, or small interfering RNA (siRNA) from the organism or environment induces the degradation of complementary messenger RNA.[1] Other classes of small RNA have been identified, including piwi-interacting RNA (piRNA) and its subspecies repeat associated small interfering RNA (rasiRNA). Small RNA "is unable to induce RNAi alone, and to accomplish the task it must form the core of the RNA–protein complex termed the RNA-induced silencing complex (RISC), specifically with Argonaute protein".
Small RNA have been detected or sequenced using a range of techniques, including directly by MicroRNA sequencing on several sequencing platforms, or indirectly through genome sequencing and analysis. Identification of miRNAs has been evaluated in detecting human disease, such as breast cancer. Peripheral blood mononuclear cell (PBMC) miRNA expression has been studied as potential biomarker for different neurological disorders such as Parkinson's disease, Multiple sclerosis. Evaluating small RNA is useful for certain kinds of study because its molecules "do not need to be fragmented prior to library preparation".
Discovery
[edit]The first sRNA discovered was in 1984 where MicF was found to regulate the outer cell membrane in E. Coli by inhibiting the production of the protein ompF and ompC.[2] The use of sRNA in regulation of gene expression was found alongside it's discovery. It was later discovered to be present across all eukaryotic organisms. In 1998 it was discovered that the sRNA can be transferred between organisms. It was later discovered in 2011 that sRNA are transferred from cell to cell inside an organism as well.[3]
Types of small RNA
[edit]
- microRNA (miRNA) - an RNA involved in RNAi through gene regulation as well as mRNA degradation.[4][5]
- Piwi-interacting RNA (piRNA) - an RNA that regulates the germ line, transposons, as well as histones. It also participates in the argonaute complex.[6]
- QDE-2 interfering RNA (qiRNA) - an RNA that regulates gene expression after DNA damage.[7]
- Short hairpin RNA (shRNA) - an RNA that acts similarly to miRNA, regulating gene expression via RISC.[8]
- small interfering RNA (siRNA) - an RNA that regulates both gene expression with RISC[9] and by histone modifications.[10]
- small nuclear RNA (snRNA), also commonly referred to as U-RNA - an RNA integral to the splicosome, that also stabilizes mRNA.[11]
- small nucleolar RNA (snoRNA) - an RNA regulates the rRNA as well as aiding alternative splicing. It also aids in mRNA degradation.[12]
- small rDNA-derived RNA (srRNA) - an RNA involved in multiple signaling pathways as well as the formation of Argonaute protein complexes.[13]
- tRNA-derived stress induced RNA (tiRNA) - an RNA that regulates translation by binding to ribosomes.[14]
- tRNA fragment (tRF) - an RNA fragment that regulates translation by binding to ribosomes and altering mRNA's caps. It can also combine with Argonaute protein complexes to degrade mRNA.[14]
- Y RNA-derived small RNA (ysRNA) - an RNA that aids in initiaion of DNA replication as well as preventing mRNA from degrading.[15]
In plants
[edit]The first known function in plants was discovered in mutants of Arabidopsis. Specifically with decline in function mutations for RNA-dependent RNA polymerase and DICER-like production. This impairment actually enhanced Arabidopsis resistance against Heterodera schachtii and Meloidogyne javanica. Similarly, mutants with reduced Argonaute function - ago1-25, ago1-27, ago2-1, and combined mutants with ago1-27 and ago2-1 - had greater resistance to Meloidogyne incognita. Altogether this demonstrates great dependence of nematode parasitism on plants' own small RNAs.
References
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- ^ Billi, Allison C.; Fischer, Sylvia E. J.; Kim, John K. (2018), "Endogenous RNAi pathways in C. elegans", WormBook: The Online Review of C. elegans Biology [Internet], WormBook, PMID 24816713, retrieved 2025-03-26
- ^ Mizuno, T; Chou, M Y; Inouye, M (April 1, 1084). "A unique mechanism regulating gene expression: translational inhibition by a complementary RNA transcript (micRNA)". Proceedings of the National Academy of Sciences. 81 (7): 1966–1970. doi:10.1073/pnas.81.7.1966. PMC 345417. PMID 6201848.
- ^ Zeng, Jun; Gupta, Vijai Kumar; Jiang, Yueming; Yang, Bao; Gong, Liang; Zhu, Hong (2019-04-23). "Cross-Kingdom Small RNAs Among Animals, Plants and Microbes". Cells. 8 (4): 371. doi:10.3390/cells8040371. ISSN 2073-4409. PMC 6523504. PMID 31018602.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Lim, Lee P.; Lau, Nelson C.; Garrett-Engele, Philip; Grimson, Andrew; Schelter, Janell M.; Castle, John; Bartel, David P.; Linsley, Peter S.; Johnson, Jason M. (2005-02-17). "Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs". Nature. 433 (7027): 769–773. doi:10.1038/nature03315. ISSN 1476-4687. PMID 15685193.
- ^ Iwakawa, Hiro-oki; Tomari, Yukihide (2022-01-06). "Life of RISC: Formation, action, and degradation of RNA-induced silencing complex". Molecular Cell. 82 (1): 30–43. doi:10.1016/j.molcel.2021.11.026. ISSN 1097-2765.
- ^ Wu, Xi; Pan, Yutian; Fang, Yuan; Zhang, Jingxin; Xie, Mengyan; Yang, Fengming; Yu, Tao; Ma, Pei; Li, Wei; Shu, Yongqian (2020-09-04). "The Biogenesis and Functions of piRNAs in Human Diseases". Molecular Therapy - Nucleic Acids. 21: 108–120. doi:10.1016/j.omtn.2020.05.023. ISSN 2162-2531.
- ^ Lee, Heng-Chi; Chang, Shwu-Shin; Choudhary, Swati; Aalto, Antti P.; Maiti, Mekhala; Bamford, Dennis H.; Liu, Yi (2009-05-14). "qiRNA is a new type of small interfering RNA induced by DNA damage". Nature. 459 (7244): 274–277. doi:10.1038/nature08041. ISSN 1476-4687. PMC 2859615. PMID 19444217.
- ^ Silva, Jose M.; Li, Mamie Z.; Chang, Ken; Ge, Wei; Golding, Michael C.; Rickles, Richard J.; Siolas, Despina; Hu, Guang; Paddison, Patrick J.; Schlabach, Michael R.; Sheth, Nihar; Bradshaw, Jeff; Burchard, Julia; Kulkarni, Amit; Cavet, Guy (October 2, 2005). "Second-generation shRNA libraries covering the mouse and human genomes". Nature Genetics. 37 (11): 1281–1288. doi:10.1038/ng1650. ISSN 1546-1718.
- ^ Tiwari, D.; patel, M.K. "22 nucleotide siRNAs: Emerging Players in Plant Stress Adaptation" (PDF). Biotica Research Today. 6 (5): 249–251.
- ^ Weinberg, Marc S.; Morris, Kevin V. (2016-08-19). "Transcriptional gene silencing in humans". Nucleic Acids Research. 44 (14): 6505–6517. doi:10.1093/nar/gkw139. ISSN 1362-4962. PMC 5001580. PMID 27060137.
- ^ Valadkhan, Saba; Gunawardane, Lalith S. (2013-04-30). Lindsay, Mark A.; Griffiths-Jones, Sam (eds.). "Role of small nuclear RNAs in eukaryotic gene expression". Essays in Biochemistry. 54: 79–90. doi:10.1042/bse0540079. ISSN 0071-1365.
- ^ Huang, Zheng-hao; Du, Yu-ping; Wen, Jing-tao; Lu, Bing-feng; Zhao, Yang (2022-05-12). "snoRNAs: functions and mechanisms in biological processes, and roles in tumor pathophysiology". Cell Death Discovery. 8 (1): 1–10. doi:10.1038/s41420-022-01056-8. ISSN 2058-7716.
- ^ Wei, Haibin; Zhou, Ben; Zhang, Fang; Tu, Yanyang; Hu, Yanan; Zhang, Baoguo; Zhai, Qiwei (2013). "Profiling and identification of small rDNA-derived RNAs and their potential biological functions". PloS One. 8 (2): e56842. doi:10.1371/journal.pone.0056842. ISSN 1932-6203. PMC 3572043. PMID 23418607.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b Xie, Yaoyao; Yao, Lipeng; Yu, Xiuchong; Ruan, Yao; Li, Zhe; Guo, Junming (2020-06-30). "Action mechanisms and research methods of tRNA-derived small RNAs". Signal Transduction and Targeted Therapy. 5 (1): 1–9. doi:10.1038/s41392-020-00217-4. ISSN 2059-3635.
- ^ Valkov, Nedyalka; Das, Saumya (2020). "Y RNAs: Biogenesis, Function and Implications for the Cardiovascular System". Advances in Experimental Medicine and Biology. 1229: 327–342. doi:10.1007/978-981-15-1671-9_20. ISSN 0065-2598. PMC 7363058. PMID 32285422.