RNA interference (RNAi)

History

The concept of RNA interference also denoted as RNAi has its inception coming after the injection of dsRNA (double-stranded RNA) was discovered to lead to suppressing particular highly homologous genes in sequence to double-stranded RNA. The injection was noted as done on nematode Caenorhabditis Elegans. Its worthnoting that bacterial feed expressing dsRNA to the worm from recombinant plasmids can also deliver dsRNA.The possibility of existence of the RNAi rapid sequence procces in humans is attributed to the observation on its succesful application onmice among other animals.

         1990 cosuppression of purple color in plants.

         1998 dsRNA injection in worms.

         1999 short RNAs identified in plants & RNAi shown in vitro.

         2000 RISC activity partially purified.

         2001 siRNAs & Dicer identified.

         2002 RNAi used against HIV & genome-wide RNAi screens begin.

Introduction

There are several uses of RNAi. Various organisms manage gene control through RNAi. Besides, laboratory requires it as a tool and prospective future therapy. Precise targeting of gene expression control mechanism is important as Eukaryotic cells exhibit sophistication and an environment that is significantly complex in structure. RNAi also refers to directing of gene silencing using small molecules of RNA in a group of mechanisms.

RNAi is involved in two most important types of RNAs molecule:

  1. Small interfering RNAs (siRNA).
  2. Micro-RNAs (miRNA).

RNA pol II transcribe most of the genes involved in proteins encoding inside the nucleus. It is splicing process that yield the primary RNA transcribed and which produces mRNA; mature messenger RNA.The exportation of mRNA into cytoplasm from nucleus is then completed.

It at this point that messenger RNA Ribosome catalyzed translation yields polypeptide chains that in turn produce proteins through folding. However, it is noted that silencing effects of small molecules of RNA can be found.

siRNA is a collection of regulatory small interfering RNA.They are longer double-stranded RNA derivatives  from either cells or delivered experimentally to the cell. In fact manipulation of gene expression is widely done through siRNA or dsRNA introduction.

Small RNA is also derived from miRNA which in most cases come from RNA transcripts in the nucleus. It is from the folds of RNA’s that miRNA are processed and exported as ds-miRNA to the cytoplasm

The principles of RNAi

The binding of miRNAs and siRNA to a “dicer” as a precursor to the double-strand yields endonuclease protein  which in turn produce short segments of RNA.The nucleotides length of most of the siRNA and miRNA  is estimated to be 21. “Argonaute” is a result of short double-stranded RNA binding. The result of this procces is “Guide strand” which is a selected Argonaute bound and remainder of RNA.

“RISC” also known as RNA Induced Silencing Complex  is a combination of Argonaute,other proteins and RNA.

Specific messenger RNA is bound by RISC through the directives of the siRNA.Precision of the target is achievable since its determined by  siRNA target messenger RNA pairing.There is always a perfect complemetary for siRNA to the site targeted. Messenger RNA is then degraded after its cleavage is catalyzed by the bound Argonaute.

The RISC is also directed to mRNA by the miRNA.In most cases, the “seed” which is part of miRNA pairs up with the targeted mRNA. It is worth noting that the targeting of several endogenous mRNA by miRNA   is as a result of matching imprecision. Degradation or translation inhibition of mRNA may be caused by miRNA Targeting. There is a continued revelation on the application of Argonaute and the small regulatory RNA Cofactors in biological procceses. Research shows that they are found in various living organisms that include animals, plants, bacteria and fungi.

 

 

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