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MicroRNAs are key regulators in diverse cellular pathways of
eukaryotes from cell differentiation to open development.
This presentation will explain what is known about these interesting molecules with
an emphasis on the gene structure, transcription, and processing.
Let me begin with the definition of microRNAs.
MicroRNA, miRNA for short is defined as
a single-stranded RNA of approximately 22 nucleotides in length,
which is generated by the RNAse III type enzyme from
an endogenous transcript that contains a local hairpin structure.
Shown here as examples are let-7 RNAs from C. elegans, Drosophila and human.
Highlighted in red is the mature let-7 RNA that is
processed out of one arm of the hairpin shaped precursor.
Like let-7 RNA, a number of microRNAs are conserved phylogenetically.
The degree of conservation is highest in
the mature microRNA segments but gets lower
in the terminal loop and in the base pair segments.
The length of the hairpin is approximately 85 nucleotides in animals.
But in plants, the structure and the length of the precursor is more variable.
So, what are the functions of microRNAs?
MicroRNAs act as guide molecules in post-transcriptional gene silencing.
Silencing is achieved by specific base pairing with the target messenger RNA.
When microRNAs pair only partially with the target mRNA,
they block translation of the mRNA into protein and eventually lead to mRNA decay.
When microRNAs pair with the targets perfectly,
meaning that the complementarity between
the messenger RNA and the microRNA is high enough,
the binding leads to mRNA cleavage in the middle of the binding site.
Mostly, animal microRNAs act through the former mechanism to repress translation,
whereas most plant microRNAs employed
the latter mechanism to induce endonucleolytic mRNA cleavage.
Recent reports indicated that each microRNA directly regulates hundreds of target mRNAs,
sometimes in combination with other microRNAs.
In humans, over 30 percent of protein coding
genes are believed to be regulated directly by microRNAs.
By silencing various target mRNAs,
microRNAs play key roles in
diverse regulatory pathways including many different aspects of embryonic development,
the differentiation of various cell types,
apoptosis and proliferation, hormone secretion,
and stem cell maintenance.
Importantly, the connection to tumorigenesis is becoming more apparent.