RNA RNA interference is found in most eukaryotic species.
interference is Two types of RNAs that promote interference:
mediated by 1. microRNAs are ncRNAs that are transcribed from endogenous eukaryotic genes: genes that
microRNAs or are normally found in the genome.
small- Play key role in regulating gene expression. Most commonly they inhibit translation of
interfering mRNAs by having a complementary sequence.
RNAs via an 2. Small interfering RNAs (siRNAs) are ncRNAs that usually originate from sources that are
RNA-induced exogenous, which means they are not normally made by cells (e.g. viruses or made by
silencing researchers to study gene function). The functioning of siRNAs is thought to play a key role
complex in preventing certain types of viral infections. And became important experimental tools.
How do these RNAs silence specific mRNAs?
miRNA is first synthesized as a pri-miRNA in the nucleus. Due to complementary base pairing, the
pri-miRNA forms a hairpin structure. Two proteins recognize (Drosha and DGCR8), and cleaves
both ends. Resulting in pre-miRNA. This is exported from the nucleus with aid of protein called
exportin 5.
siRNA do not go trough these processing events, but instead precursor-siRNAs (pre-siRNAs) are
derived from viral RNAs or made by researchers. Pre-siRNA is formed from two complementary
RNA molecules that base-pair with each other.
In cytosol both pre-siRNA and pre-miRNAs are cut by an endonuclease called dicer. It is cut in
double-stranded RNA molecule. This associates with proteins to form a complex = RNA-induced
silencing complex (RISC). One of the RNA strands is degraded. The remaining single-stranded
miRNA or siRNA is complementary to specific mRNAs that will be silenced. The miRNA or siRNA
acts as guide that causes RISC to recognize and bind to such mRNA molecules. After RISC binds to
an mRNA, three outcomes.
- RICS inhibit translation without degrading the mRNA. More common in miRNAs.
- The RICS-mRNA complex may remain in a cellular structure called a processing body (b-
body), where it can be stored until it is reused or degraded. Sometimes inhibition is only
temporarily.
- RICS may direct the degradation of the mRNA. One of the proteins in RICS: Argonaute,
can cleave mRNA. Usually this outcome with siRNAs, which are typically a perfect match
to their target mRNAs.
Usually expression of mRNA is permanently silenced. The effect is termed RNA interference: the
miRNA or siRNA interferes with the proper expression of an mRNA,
In addition to mRNA degradation, siRNAs can inhibit transcription by causing chromatin
remodelling modifications. This effect is also seen with another type of small regulatory RNA:
PIWI-interacting RNA (piRNA).
Powerpoint Some genes do not encode polypeptides, but are transcribed into non-coding RNAs (ncRNAs).
Estimates of the number of ncRNAs in humans range from several thousand to tens of
thousands. In textbooks, RNA has been historically studied for its role in making proteins.
This chapter focuses on the role of ncRNAs, which perform a spectacular array of cellular
functions in bacteria, archaea, and
eukaryotes.
Common • In most cell types, ncRNAs are
binding more abundant than mRNAs.
interactions • In a typical human cell, only
between about 20% of transcription
ncRNA and involves the production of
other mRNAs, whereas 80% of it is
molecules. associated with making
ncRNAs.
ncRNAs Can Bind to Different Types of
Molecules
RNA molecules can form stem-loop
structures, which may bind to pockets
on the surface of proteins.
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