My gene expression in the higher organisms.

My research plan
is about finding a relation between gene silencing and body temperature of
organisms. Body temperature depends on various life activities happening inside
the cell, and it influences various life functions, such as behavior, nerve
activity, and cellular metabolism. However, in many cases regulatory mechanisms
depending on the temperature are not known. In my planned research topic, I will
aim to uncover the molecular mechanism of gene expression dependent on
temperature, which are caused by properties of nucleic acids, especially
focused on the temperature-gene expression relation of non-coding RNAs. For a long time,
function of a gene was analyzed to be based on only transcription and
translation. However, the recent transcriptome data shows that many non-coding RNAs
are expressed from the genome and they are involved in various functions that have
not been fully discovered.


A short
non-coding RNA molecule called microRNA suppresses the messenger RNA in a
process called RNA silencing. Although microRNA does not exist in common organisms
such as Escherichia coli, or Saccharomyces cerevisiae, it exists in
the higher organisms, such as mouse. In fact, human microRNA is involved not
only in development or differentiation but also in the complicated functions of
the nervous system or severe diseases like cancer. So, RNA silencing is now an
essential mechanism that cannot be ignored in understanding the regulatory
mechanisms of gene expression in the higher organisms.

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silencing, microRNA forms base pairing with messenger RNA by having a
complementary nucleotide sequence and suppresses gene expression. In the Ui-Tei
laboratory, it was reported that the efficiency of RNA silencing depends on the
stability of base pairing of messenger RNA and the microRNA (Kamola et al.,
PLoS Comput. Biol. 2015; Hibio et al Sci. Rep. 2012; Ui – Tei et al. Nucleic
Acids Res. 2008). It is well-known that the thermodynamic properties of the
stability of base-pairing of nucleotides are affected by temperature.
Therefore, an interesting hypothesis was introduced that gene suppression
efficiency by RNA silencing changes when the body temperature of an organism
changes. They examined the possibility of this hypothesis using bioinformatics,
in advance. MicroRNAs of many organisms are registered into a microRNA
database. For the microRNAs from a number of organisms, the average stability
of base pairing between microRNA and target messenger RNA was defined as
melting temperature (Tm value). As a result, it was revealed that the melting
temperature value of the organism with a high body temperature was high, and
the Tm value of the organism with the low body temperature was low. So, it was
suggested that each organism evolves conserving microRNAs with appropriate
suppression effects depending on their growth temperature. Based on the results
shown in the Ui-Tei laboratory, I plan to uncover the mechanism by which
systematic gene silencing by microRNA is regulated by growth or environment
temperature. To sum up, this research is expected to lead to the elucidation of
the molecular mechanism of human diseases or temperature-dependent life
activities, and development of therapeutic methods.