Biogenesis AUB protein plays a similar role

Biogenesis of piRNA


The main distribution sites piRNA are the animal testes
spermatogonial cells and ovarian oocytes and in drosophila follicle cells (somatic
cells). There are two main pathways of the piRNA biogenesis: In germ cells, the
AUB dependent piRNA pathway (secondary piRNA processing) is active, while in somatic
cells, only pathway for producing piRNAs is the PIWI dependent pathway (primary
piRNA processing) (15). The primary antisense transcripts of piRNA are
preferably loaded onto PIWI protein. This complex is called as piRISCs
(piRNA-induced silencing complexes) which breaks the sense transcript of transposons
at positions 10 and 11 and generate the 5′ end of a sense Ago3-associated
piRNA. In the AUB dependent pathway that is known as the Ping-Pong cycle,
proteins of AUB and Argonaute 3 (AGO3) are involved (16). The AUB protein plays a similar role to PIWI and
forms the 5? end of piRNAs that associated with AGO3. This complex produces the
5? end of the antisense piRNAs by the cleavage of antisense piRNA precursors
and then these are loaded onto AUB (17). The HEN1 protein mediated 2??O-methylation
of the 3? end of piRNA. Also, Mili and Miwi2 are two members of the mouse Piwi
proteins that by processing of transposable elements (TEs) produce piRNAs. This
occurs in cytoplasmic granules called pi-bodies and piP-bodies (18).

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The role of piRNAs in male infertility


The piRNAs can play different
roles in biological processes, including: Sex Determination, Gene Silencing,
Epigenetic Regulation and Cancer. Their most important role is to
protect the gametes genome from the transposon invasion and is performed by
PIWI-piRNA complexes with silencing their transcripts (17). Consequently, piRNAs are usually used in the genome,
but the aberrant expression of each of the genes involved in biogenesis and
function can lead to modifications in the genome and different disorders.  One of these disorders is male infertility. In Figure 1, the most important research performed on
male infertility and piRNAs is summarized:

The Moloney leukemia virus 10-like 1 (MOV10L1) gene is
a piRNA biogenesis- related gene that plays a role in the primary and secondary
processing (19). It can help to primary piRNAs for binding to the PIWI
protein. Some studies have confirmed that several polymorphisms of this gene
have a remarkable increase in infertile men (20). In human, the association of four human PIWI proteins
(HIWI, HILI, HIWI2 and PIWIL3) in male fertility has been shown. In 2010 and
2017, investigations on Chinese and Iranian populations with non-obstructive
azoospermia revealed independently a relationship between HIWI2 rs508485 (T>C)
and non-obstructive azoospermia and this variant can be considered as a risk
factor for male infertility (21, 22).

A recent study on
peripheral blood samples of 30 infertile men, showed
that rs10773767 and rs6982089 were two single nucleotide
polymorphisms (SNPs) in PIWIL1 and
PIWIL2 respectively. These polymorphisms were allele-specific
methylation-sensitive and suggests that DNA methylation changes in these genes
are associated with spermatogenesis disorders (23).

Furthermore, Transposons are repetitive elements that
use the genome of a host cell to survive and amplification. For protecting of
the genomes of gametes from their invasion, PIWI-piRNA complexes target them to
silence of their transcripts. LINE-1 (L1) is one of the transposons studied
that by performing the examinations on patients with cryptorchidism revealed that
a consequence of alterations in the Piwi-pathway and derepression of
transposable elements in these patients is infertility (24). These studies indicate that piRNAs may play a crucial role in male infertility.


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