1 Int. J. Biomol. Biomed.

International Journal of Biomolecules and Biomedicine (IJBB)

ISSN: 2221-1063 (Print), 2222-503X (Online)
http://www.innspub.net
Vol. 5, No. 3, p. 1-12, 2016

RESEARCH PAPER OPEN ACCESS

Micro RNA genes and their likely influence in rice (Oryza sativa L.)
dynamic traits through evolution

Justine Kitony*

Kenya Agricultural and Livestock Research Organization (KALRO), Mwea, Kenya

Key words: Evolution, Gene regulation, Biogenesis, Micro RNA (miRNA).

Article Published: 17 November 2016
Abstract

Micro RNAs (miRNAs) are small non-coding RNAs molecules having approximately 18-25 nucleotides, they are
present in both plants and animals genomes. MiRNAs have diverse spatial expression patterns and regulate
various developmental metabolisms, stress responses and other physiological processes. The dynamic gene
expression playing major roles in phenotypic differences in organisms are believed to be controlled by miRNAs.
Mutations in regions of regulatory factors, such as miRNA genes or transcription factors (TF) necessitated by
dynamic environmental factors or pathogen infections, have tremendous effects on structure and expression of
genes. The resultant novel gene products presents potential explanations for constant evolving desirable traits
that have long been bred using conventional means, biotechnology or genetic engineering. Rice grain quality,
yield, disease tolerance, climate-resilience and palatability properties are not exceptional to miRN Asmutations
effects. There are new insights courtesy of high-throughput sequencing and improved proteomic techniques that
organisms’ complexity and adaptations are highly contributed by miRNAs containing regulatory networks. This
article aims to expound on how rice miRNAs could be driving evolution of traits and highlight the latest miRNA
research progress. Moreover, the review accentuates miRNAs grey areas to be addressed and gives
recommendations for further studies.
*Corresponding Author: Justine Kitony  kjusto@gmail.com.

Justine Kitony
2 Int. J. Biomol. Biomed.

Introduction Moreover, there is limited information about rice

Rice has two main classes of small RNAs: microRNAs miRNAs despite clear demonstrations that they play
(miRNAs) and small interfering RNAs (siRNAs). crucial roles in improving rice agronomic traits
MiRNAs are derived from endogenous single stranded (Macovei et al., 2012). Present review gives an update
transcripts that fold back to themselves, contrary to of rice miRNAs.
siRNAs which originate from longer exogenous double-
stranded RNA taken by cell from vectors like virus (Guo Rice productivity mainly depends on genome
et al., 2015; Martinez de Alba et al., 2013). However, stability, due to its sessile nature, several external
both small RNAs are involved in epigenetics using RNA- factors (UV light, drought, heavy metals and pathogen
induced transcriptional silencing (RITS) as well as key infections) influences rice genome stability. Different
players in RNA interference (RNAi) process which is visible traits in rice varieties are essentially caused by
important for plant cell survival under various stresses gene expression variation rather than gene products
(Deng et al., 2015;Younis et al., 2014). Typically miRNAs structure changes. MiRNA-mediated gene expression
associate with mRNA via complementary base pairing
regulations have largely been employed to withstand
to influence stability of mRNA. MiRNAs achieve these
dynamic external changes. These adaptation
key regulatory functions by coupling with Argonaute
mechanisms are greatly achieved through constant
(AGO) proteins to form a unit that degrade target
evolution with gain or loss of miRNA binding sites
messenger RNA (mRNA). Although degradation is the
caused by nucleotide mutations. Plants miRNAs have
main mode of miRNA operations to attain regulatory
been characterized to evolve through target genes
functions, regulation can also achieved through mRNA
inverted duplications, random formations or via
translation repression or direct DNA methylation
modification of existing miRNAs (Allen et al., 2004;
(Jones-Rhoades, 2006; Sun, 2012).
Felippes et al., 2008; Guo et al., 2008). Nevertheless,
plants miRNAs are generally conserved with the novel
In recent years, rice miRNAs have been catalogued to
miRNAs expunged in a short evolutionary period
be involved inpanicle branching, increased yield,
because it’s deleterious nature (Cuperus et al., 2011).
improved grain quality, early flowering, immunity to
diseases, among other important traits at post-
Biogenesis of miRNAs
transcriptional level (Baldrich and San Segundo,
miRNA biogenesis is a diverse complex process
2016; Chen et al., 2013; Miura et al., 2010; Wang et
accompanied with many regulatory proteins and
al., 2012; Zhang et al., 2013). Altering miRNAs
enzymes in a series of steps (Wen-wen et al., 2014).
activities leads to direct physiological variations in
plants where they act as ubiquitous regulators in the In summary, the processes begin with miRNA gene

genes expression. The latest version of important being transcribed into a primary miRNA (pri-miRNA)

miRNA database - miRBase 21 (Released on June, controlled by Polymerase II enzymes (Lee, 2004;

2014) stores 28645 entries representing hairpin Wang et al., 2013).

precursor miRNAs, in which 592 precursors and 713

Thereafter, dicer-like1–serrate–hyponastic leaves 1
mature miRNAs are from rice (Oryza Sativa L.).
(DCL1-SE-HYL1) microprocessor complex
Studies of miRN As has greatly advanced since it was
(Baranauske et al., 2015) processes pri-miRNA to a
first documented in Caenorhabditiselegans (Lee et al.,
stem loop intermediate called pre-miRNA containing
1993; Reinhart et al., 2000). The adoption of high
miRNA/miRNA* duplex because of their self-
throughput sequencing for genome discovery and
complementary foldback structure. Consequently,
analysis has identified plethora of miRNAs in plants.
However, few miRNAs are fully characterized (Wang HYL1, a double-stranded RNA binding protein, help

et al., 2004). in the metabolism stability (Han et al., 2004).

Justine Kitony
3 Int. J. Biomol. Biomed.

Henceforth, the miRNA/miRNA* duplex is cleaved before mature miRNA guide strand is selected, strand
into approximately 21nt miRNA at nucleus by DCL1 with lower thermodynamic relative to miRNA* and
(Park et al., 2002) with few exceptions from miRNAs enhanced by the already associating RNA binding
which require other DCL family members for proteins is preferentially selected (Eamens et al.,
biogenesis: DCL2 generates 22nt, DCL3 generates 2009) while the opposite (passenger) strand is
24nt and DCL4 generates 21nt miRNA (Deleris et al., removed due to conformational changes at AGO1
2006; Rogers and Chen, 2013) thereafter miRNA is complex influenced by dissociation of Heat Shock
exported by HASTY/nuclear pore exports to Protein(HSP90) and SQUINT (SQN). Immediately
cytoplasm (Wu et al., 2010). As showed in Fig. 1. after interacting with all necessary components RISC
double-stranded miRNA is loaded into RNA-induced complex guided by miRNA direct mRNA activity
silencing complex (RISC), subsequently the miRNA (gene silencing) (Bartel, 2004; Iki et al., 2010;
duplex unwinds facilitated by helicase-like enzyme Schwarz, 2003).

Fig. 1. Biogenesis of plants miRNA.

Plants miRNA biogenesis however have additional step To recap biogenesis process, mature miRNA guide
compared to animal miRNA biogenesis. The strand, often the strand with weaker 5` terminus, is
miRNA/miRNA* duplexes are 2’-O-methylated on the retained in RISC complex where it associates with
ribose of the last nucleotide by miRN Amethyl argonaute protein and other proteins complexes to
transferase HEN1, which protect the 3’ end from mediate activity of target mRNA (Rajagopalan et al.,
uridylation and degradation (Li et al., 2005).
2006). The opposite miRNA strand also known as
passenger strand is degraded or loaded into another
It’s worth noting that for rapid change of expression
RISC in non-canonical miRNA pathways (Eamens et
profiles, exoribonucleases encoded by Small RNA
Degrading Nuclease (SDN1) enzyme known for al., 2012; Ramachandran and Chen, 2008; Wen-wen

degradation is necessary for mature miRNA turnover. et al., 2014).

Justine Kitony
4 Int. J. Biomol. Biomed.

miRNAs mechanisms of action Translational inhibition in plants can also be achieved

Although the specific AGO proteins to be associated, when miRNA are in perfect complementation with
location and action to be taken remains unclear, targets unlike in animals where it is often associated
plants miRNA generally interact with DCL and AGO with limited miRNA/target complementation (Zeng et
proteins to form effector complexes. The associated al., 2003). Overexpressed miR172 in Arabidopsis
proteins in RISC complex guided by miRNA target mutants demonstrated hindered proteins levels but
mRNA or chromatin which is highly complementary in not mRNAs, this event corroborates that translation

transcripts sequence thus destabilizing through slicing, inhibition occurred rather than cleavage (Aukerman

translational repression or chromatin modification and Sakai, 2003; Dugas and Bartel, 2008).

mostly at posttranscriptional level. (Eamens et al., 2008;

Roles of miRNAs
Wu et al., 2009). Notwithstanding that, miRNAs can
Breeding elite rice is a global objective to sustain human
also silence at transcriptional level via DNA methylation
population which its growth has outpaced rice
demonstrated by rice DCL3-dependent 24nt miRNA
production (3K RGP, 2014). The proposal of designing
which is loaded into AGO4 and direct methylation at the
ideal plant architecture (IPA) was bold move by rice
nucleus (Wu et al., 2010).
scientists aimed at enhancing yield through point
mutations of regulatory factors. Altering activity of
AGO1 deems sufficient for miRNA mediating
Osmir156 which target SOUAMOSA PROMOTER
degradation in plants (Baumberger and Baulcombe,
BINDING PROTEIN-LIKE 14 (OsSPL14) displayed rice
2005). AGO1 activity vastly depends on SQUINT
with increased yield, good quality and stress tolerance
(SQN) which encodes orthologue of Cyclophilin 40
(Jiao et al., 2010; Miura et al., 2010).
(Cyp40) and Heat Shock Protein 90 (HSP90) (Smith
et al., 2009). Rice (Oryza Sativa L.) plant has four
The responses to dynamic environment prompting
AGO1 homologs (AGO1a, AGO1b, AGO1c and AGO1d)
appropriate traits and survival strategies by cells is
(Carbonell et al., 2012). Whilst, AGO2 associates with
believed to be guided by miRNAs (Xiu-JieWang,
mir408 for defense actions against pathogen 2004). Regulatory roles in biological processes under
(Maunoury, 2011), AGO7 interacts with miR390 to influence of miRNA is highly conserved in plants, this
regulate cellular signaling (Endo et al., 2013), AGO10 is evidenced by the fact that most miRNA families are
involves recruiting mir165/mir166 to regulate species specific (Kamanu et al., 2013).
development (Zhou et al., 2015). Interestingly, the
diverse AGO proteins family cross talk initiating Multiple miRNA have also been manifested to play
alternative RNA-mediated defenses. For example, integral role in rice immunity against rice blast, a fungal
mir403 disassociated with AGO1 to activate defense disease caused by Magnapor the Oryza. The counter
pathway mediated by AGO2 thus countering viral measures employed by rice against fungus infection is
suppression (Harvey. et al., 2011). effected at Pathogen-associated molecular patterns
triggered immunity (PTI) (Li et al., 2010) and effector
It is elucidated that miRNAs in animals, which are triggered immunity (ETI) levels (Mentlak et al., 2012).
partially complementary to the target mRNA can also Basal responses in PTI showed mir398b mediating
accelerate deadenylation hence rapid mRNAs regulation of multiple genes: Os03g22810 encoding
degradation (Eulalio et al., 2009). High slicing activity Superoxide Dismutase (SOD), Os07g46990 encoding
and redundancy within deadenylase families in plants SOD2 and Os04g48410 encoding copper chaperone for
makes it difficult to experimentally ascertain slicing- SOD displaying reduced fungal growth and increased
independent target deadenylation (Wang et al., 2013). hydrogen peroxide at the infection site. When pathogens
However, accumulation of cleavage products in most successfully delivered effectors to suppress responses at
miRNA targets symbolizes some sort of slicing PTI, alternative rice defense mechanism was recorded to
independent destabilization (German et al., 2008). be activated. (Li et al., 2014).

Justine Kitony
5 Int. J. Biomol. Biomed.

Apart from basal regulations, rice miRNA also act as When plants were subjected to drought stress,
positive regulator. Expressions of mir160a displayed phytohormoneabscisic acid (ABA) worked contentiously
up-regulation only in resistant rice lines, the target with phytohormone auxin generally regulated by
Os04g43910 gene encoding Auxin Response Factor 16 miR393 enhancing lateral root growth, transcripts
(ARF16) showed decreased expression. This indicates encoding two auxin receptors, TIR1 and AFB2 were
positive regulation of immunity against pathogen cleaved by the miRNA (Chen et al., 2012; He and Li,
through suppression of indole-3-acetic acid (IAA) 2008).
pathways (Li et al., 2014).
To sum up, predictions of miRNA targets (BOX 1) have
revealed many regulatory pathways that might be
Moreover, miRNAs have been demonstrated to be
mediated by miRNA (He and Hannon, 2004) indeed
involved in stabilizing or destabilizing gene expressions
miRNA are involved in almost all biological process
depending on the mRNA effects (Xie et al., 2007) It is
directly or by feedback regulation of miRNA products.
vividly clear from the first 20 experimentally discovered
rice miRNAs to the novel miRNA that they play crucial Evolution of miRNAs
role in development and abiotic stress mitigation Advances in high throughput sequencing, have brought
therefore influencing growth (Jia-Fu Wang, 2004; new insights into how the evolution of miRNA-
Sunkar et al., 2008; Xie et al., 2006). containing regulatory networks contributed to species
complexity. Although, plants miRNAs are under
Further Research using model plant (Arabidopsis purifying selection, computational sequence analysis
thaliana), verified that miRNA is controlling gene on regions outside miRNA/miRNA* duplex of ath-
regulation systems via the target genes. For this reason, miR161, ath-miR163 and ath-miR822 showed some
there is often positive correlation between miRNA correlation with the evolved target sequences. The
regions and target genes sequence. (Carrington and miRNA sequences were aligned in inverted form to
Ambros, 2003; Takuno and Innan, 2008). When target genes, asserting that inverted duplications was
Arabidopsis thaliana was subjected to abiotic stresses, probably the cause of the new miRNAs genes (Allen et
miRNAs among them; miR168, miR171, and miR396 al., 2004; Ehrenreich and Purugganan, 2008).
responded to the high-salinity, drought, and low
temperature stresses, showing great sense of cross-talk Mutations in miRNA-related regions, basically
in the signaling pathways (Liu et al., 2008). initiated different phenotypes observed in plants,
altering biological functions thus enhancing genome

Most miRNA in plants mediate gene silencing of the evolution. It is therefore likely that mutations in the

target mRNA by base pairing in almost perfect inverted regions could be speed up formation of new

manner hindering translation rather than slicing, miRNAsgenes (Cuperus et al., 2011; Sun et al., 2009).

miR-172 elucidated this phenomenon in Arabidopsis:

In the quest to find out whether miRNAs have
base pairing complementarity with APETALA 2 (AP2)
evolved during domestication of rice, it was found
located in the coding region instead of the 3′ UTR
that some miRNA genes evolve rapidly most likely
therefore controlling cell-fate specification in flower
due to strong negative selection (Liu, 2013). osa-
development (Chen, 2004) By the same token,
smR5864w gene in rice showed that, a single C-to-G
miRNA 39 was involved in root development and
point mutation was the cause of pollen fertility or
hormone signaling, cleaving mRNA targets which
sterility (Zhou et al., 2012).
encoded Scarecrow-like (SCL) family (Llave, 2002).

During evolution, newly formed miRNAs get

Importantly, expression patterns of miRNAs support
expressed weakly therefore face negative selective
their roles not only in development but also in response
pressures to evolve rapidly compared to conserved
to biotic/abiotic stresses.
miRNAs.

Justine Kitony
6 Int. J. Biomol. Biomed.

Interestingly, approximately one third of miRNAs During the co-evolution of miRNAs and target genes,
likely increase the processing of pre-miRNAs into nucleotide polymorphism played a crucial role in
mature miRNAs, due to polymorphisms at miRNA determining gain or loss of miRNA binding
stem region hence enhancing the stability of hairpin sites.(Berezikov, 2011) in order for a miRNA to be
structures (Liu, 2013). active, there should be insignificant nucleotides
variation between miRNA and target binding sites:
The evolution of miR395 gene families in both
mir161 and mir163 genes of Arabidopsis thaliana
Arabidopsis Thaliana and Oryza Sativa plants
demonstrated that inverted duplication activities
demonstrated the homology that exist in miRNA gene
coupled with expansion of target gene families which
members, which came as a result of gene duplications
are adopted into miRNA biogenesis pathways greatly
events at different time scales during evolution. The
affected its evolution(Allen et al., 2004).
evolution of plants miRNA gene was similar to
protein-coding genes, plants have smaller number of
Strategies for characterizing miRNAs
unique miRNA sequences but larger miRNA families
(Li and Mao, 2007). . MiRNA functional characterization can be achieved
using genetic mutations, metabolism changes brought
To put miRNA family evolution into perspective, rice by mutations of miRNA have tendency to result in
miR395 displayed 24 genes transcribed as a single pleiotropic developmental defects, increased grain
transcript from the four compact clusters. Apparently, productivity among other important traits in plants (Jiao
the variation of genomic organizations of miR395 et al., 2010; Miura et al., 2010; Palatnik et al., 2003).
gene families, and other miRNA gene families Defects of miR-JAW gene activity which is homologous
generated different regulatory profiles in plants (Li to CINCINNATA (CIN) gene (Nath, 2003) showed
and Mao, 2007). crinkly leaves, the uneven leaf curvature and shape was
concluded to be caused by miRNA activity on several
Lastly, transposable elements could also be speeding Teosinte branched1; Cycloidea; Proliferation cell factor1
up miRNA genes evolution, along with rapid genetic
(TCP) genes which controlled leaf development in
recombination at the origin of gene structures. In the
Arabidopsis (Palatnik et al., 2003).
case of long terminal repeat retro transposons (LTR-
RT), research elucidated that when subjected to
mutation, LTR-RT formed miRNA-like hairpins that Tampering with Auxin homeostasis regulated by

eventually became miRNA genes that led genome miRNA in Arabidopsis led to down regulation of
evolution dormancy (Zhou et al., 2013). auxin signals responsible for lateral root development
(Eckardt, 2005; Guo et al., 2005). Overexpression is
MiRNA-target evolution another strategy employed when profiling miRNAs,
In order to understand miRNA target evolution, Overexpressed miR444a resulted in reduced tillers in
analysis of evolution of miRNA binding sites is rice (Guo et al., 2013).
necessary. Plants have highly conserved miRNA
binding sites and strong evolutionary selection,
Moreover, subjecting the study plants to stresses
miR397 for example was hereditary retained in dicots
like drought, salinity and hydrogen peroxide
to target L-ascorbate oxidase precursors (Jones-
subsequently documenting miRNA differential
Rhoades and Bartel, 2004).
expressions and physiological changes is
Using molecular evolution and population genetics to indisputable way to characterize them; when rice
study miRNA target genes and binding site in rice was exposed to cadmium (Cd) stress various
genome, a study revealed that loss in activity of responses were observed, there was a single up-
miR397 after the whole genome duplication (WGD) regulated gene while 18 of the genes down-
was due to mismatches in the likely miR397 binding regulated, miRNAs were concluded to play a major
site to Os01g62600 gene (Guo et al., 2008). role in Cd tolerance (Ding et al., 2011).

Justine Kitony
7 Int. J. Biomol. Biomed.

Conclusions and recommendations Diligent use of gene conservation knowledge should

This review highlights the recent miRNAs research also be observed keenly while doing miRNA research,
findings. Until now, hundreds of plant miRNAs have this is necessary since studies have shown contrasting
been identified by next generation sequencing (NGS) findings on similar miRNAs, there is likely a diverse
and computational approaches. However, the omics of outcomes between dicots and monocots plants innate
rice miRNAs still lags behind other plant research areas. immunity regulation as well as other biological
The complex networks and relationships among processes(Li et al., 2014; Li et al., 2010).
transcription factors, miRNAs, miRNA targets and other
regulatory components remain to be fully explored. Never has miRNA research been more exciting with
the extensive characterization of miRNA/targets in
Limited comparative data has been big hindrance to the non-model plants using in-silico techniques coming
establishment of birth and evolution of plants miRNAs. up with promising results. MiRNA, siRNA and other
The alternative low depth cloning techniques used in non-coding RNAs based applications will definitely be
profiling miRNAs is apparently biased to highly of great use if optimized fully as gene resource factory
expressed regions. Vital questions raised on mechanisms for crop improvement.
of miRNA co-evolution with their targets are yet to be
extensively answered (Luo et al., 2013). In order to achieve compressive understanding of the
evolution of miRNA-mediated regulatory pathways
Although, there is tremendous amount of research
under physiology and stresses, we anticipate many
being conducted in all the frontiers of coding and
future studies focused in examining the molecular
non-coding RNA molecules using point mutations,
mechanisms and regulatory roles of miRNAs in stress
artificial miRNAs engineering or inhibition of miRNA
tolerance and relationship to other biological
activity by target mimicry (Debat and Ducasse, 2014)
processes.
.We anticipate more research work to deliver and
improve the precision of important agronomic traits
like climate-resilience and high nutritional value Acknowledgement

which will go a long way in helping malnutrition in Many thanks to anonymous referees whose constructive

the world (Ye, 2000). comments were helpful in improving this review paper.

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