Double-stranded RNA explained

Double-stranded RNA (dsRNA) is RNA with two complementary strands found in cells. It is similar to DNA but with the replacement of thymine by uracil and the adding of one oxygen atom. Despite the structural similarities, much less is known about dsRNA.^[1]

They form the genetic material of some viruses (double-stranded RNA viruses). dsRNA, such as viral RNA or siRNA, can trigger RNA interference in eukaryotes, as well as interferon response in vertebrates.^{[2] [3] [4]} In eukaryotes, dsRNA plays a role in the activation of the innate immune system against viral infections. ^[5]

History of discovery

Watson and Crick had noted early on that the 2′ hydroxyl group on each RNA nucleotide would prevent RNA from forming a double helix similar to the one they had described for DNA. ^[6]

In 1995, Alexander Rich and David R. Davies propose the double helix structure of RNA for the first time. ^[7]

Structure

High molecular weight RNA in the 'A' form is referred to as dsRNA and possesses the following characteristics:

• A cooperative type of temperature transition profiles with ionic strength-dependent Tm values;
• Sedimentation coefficients (s_20,w) above 8–9 S;
• A base composition expected for an RNA duplex composed of two complementary, antiparallel strands stabilized by hydrogen bonds and hydrophobic interactions;
• A molar absorbance (per phosphodiester group) lower than that of single-stranded RNA (ssRNA).
• An absolute hypochromicity significantly more than ssRNA; ^[8]

These characteristics are found in the genomes of various organisms, as well as in the double-stranded RNA that was formerly referred to as the "replicative form" and subsequently thought to be a byproduct of phage RNA replication. Alternatively, they are found in artificial high molecular weight double-stranded polyribonucleotide complexes like poly(A) · poly(U) or poly(I) · poly(C) complexes.

The widely recognized acidic forms of polyadenylate and polycytidylate can be introduced to these canonical double-stranded RNA species. Because the bases of these polyribonucleotides are protonated at pH values lower than adenine and cytosine's pK values, they assume a well-characterized [and for poly(A) particularly stable] double-stranded structure at acidic pH levels.

The more or less abundant self-complementary sequences found in all other forms of RNA, including rRNA, mRNA, tRNA, single-stranded viral RNA, and viroid RNA, can likewise form double-helical secondary structures, albeit incomplete and/or irregular.

Sources

Endogenous retroviruses, natural sense-antisense transcript pairs, mitochondrial transcripts, and repetitive nuclear sequences, including short and long interspersed elements (SINEs and LINEs), are some of the primary sources of endogenous dsRNA.^[9]

Properties

In general, dsRNAs share some significant characteristics:

• They show a remarkable resistance to RNase A.
• They are not transcribed from the DNA of the host genome.
• The majority of them are consistently present in the host at a low concentration.
• They do not appear to have a noticeable impact on the phenotype of their host.
• They are effectively carried to the next generation.

dsRNA range in size from 1.5 to 20 kbp. Smaller dsRNAs (<2.0 kbp) are frequently associated with virus-like particles, and some of these dsRNAs have already been identified as viruses belonging to the Partitiviridae family. They typically have two distinct linear dsRNA segments, each approximately 2.0 kbp in length. Segments larger than 10 kbp are unlikely to be linked to specific virus-like particles, as no unique virus-like particles have been identified in samples prepared using various purification techniques. For this reason, these large dsRNAs were previously referred to as enigmatic dsRNAs, endogenous dsRNAs, or RNA plasmids.^[10]

Notes and References

1. Lipfert J, Skinner GM, Keegstra JM, Hensgens T, Jager T, Dulin D, Köber M, Yu Z, Donkers SP, Chou FC, Das R, Dekker NH . Double-stranded RNA under force and torque: similarities to and striking differences from double-stranded DNA . Proceedings of the National Academy of Sciences of the United States of America . 111 . 43 . 15408–15413 . October 2014 . 25313077 . 10.1073/pnas.1407197111 . free . 4217419 . 2014PNAS..11115408L .
2. Schultz U, Kaspers B, Staeheli P . The interferon system of non-mammalian vertebrates . Developmental and Comparative Immunology . 28 . 5 . 499–508 . May 2004 . 15062646 . 10.1016/j.dci.2003.09.009 .
3. Weber F, Wagner V, Rasmussen SB, Hartmann R, Paludan SR . Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses but not in detectable amounts by negative-strand RNA viruses . Journal of Virology . 80 . 10 . 5059–5064 . May 2006 . 16641297 . 1472073 . 10.1128/JVI.80.10.5059-5064.2006 .
4. Jana S, Chakraborty C, Nandi S, Deb JK . RNA interference: potential therapeutic targets . Applied Microbiology and Biotechnology . 65 . 6 . 649–657 . November 2004 . 15372214 . 10.1007/s00253-004-1732-1 .
5. Whitehead KA, Dahlman JE, Langer RS, Anderson DG . Silencing or stimulation? siRNA delivery and the immune system . Annual Review of Chemical and Biomolecular Engineering . 2 . 1 . 77–96 . 2011-07-15 . 22432611 . 10.1146/annurev-chembioeng-061010-114133 .
6. Salazar M, Fedoroff OY, Miller JM, Ribeiro NS, Reid BR . The DNA strand in DNA.RNA hybrid duplexes is neither B-form nor A-form in solution . Biochemistry . 32 . 16 . 4207–4215 . April 1993 . 7682844 . 10.1021/bi00067a007 .
7. Zhang S, Wittig B . Alexander Rich 1924-2015 . Nature Biotechnology . 33 . 6 . 593–598 . June 2015 . 26057974 . 10.1038/nbt.3262 .
8. Book: Libonati M, Sorrentino S. Degradation of Double-Stranded RNA by Mammalian Pancreatic-Type Ribonucleases . 2001 . Methods in Enzymology . 341 . 234–248 . 2024-06-07 . Elsevier . 10.1016/s0076-6879(01)41155-4 . 11582780 . 978-0-12-182242-2 .
9. Sadeq S, Al-Hashimi S, Cusack CM, Werner A . Endogenous Double-Stranded RNA . Non-Coding RNA . 7 . 1 . 15 . February 2021 . 33669629 . 7930956 . 10.3390/ncrna7010015 . free .
10. Book: Fukuhara T, Moriyama H . Endornavirus . Mahy BW, Van Regenmortel MH . Encyclopedia of Virology . 2008 . Elsevier/Academic Press . Amsterdam . 978-0-12-374410-4 . 3rd.