Introduction:

Transcription factors(TFs) and their interaction withpromoter regulatory sequences are necessary to regulate gene expression in plants and animals. There are about 2500 genes in Arabidopsis genome encode for various transcription factors (1). There are large numbers of transcription factors related to regulation of genes in plants. The main families include NAC {No apical meristem (NAM), Arabidopsis transcription activation factor (ATAF), Cup-shaped cotyledon (CUC)}. Various isoforms of NAC family have beenrecognizedand categorized inmodel plants like Arabidopsis(2,3),crops like Oryza sativa(4,5)soybean (Glycinemax) (6,7,8) and wheat (Triticum species) (9)and in certaintypical tree classes like Populustrichocarpa (10) and citrus (Citrus sp.) (11,12).Extensive research supported by the study of genomic sequences of various plants identified 117 NACgenes in Arabidopsis, 79 in Vitisvinifera, 151 in rice, 163 in Populustrichocarpa and 152 in tobacco and soybean, making them a major group of TF’s in plants.

Structural characteristics:

Typically, NAC proteins consist of two motifs located at both N and C- termini. N-terminal motif is conserved and comprise of 150 amino acids while C-terminal transcription regulatory (TR) regions are highly variable (Figure 1 (i))(13). Along with these structural motifs, some uncommonmodifications in NAC assembly has also been observed [Fig 1 (ii–vi)]. One domain of NAC codes for 1 NAC protein(14,15) and two tandem repeated NAC domains(16). SOG1 genes are extended by the N-terminal motif (16,17) and are made up of NAC and Vascular plant One-Zinc finger proteins, which includes DNA binding (db), zinc finger, C-terminal NACregion and N-terminal TR region(13,16).

NAC domains:

NAC domain is recognized by its DNA binding ability and is divided into 5 subdomains (A-E, Fig 1). Each subdomain is highly conserved and have diverse properties related to structure. Functional analysis revealthat subdomain A is involve in the synthesis of functional dimer, subdomain B and E are distinct and shows the functional variation in NAC genes in different plants. Subdomain C contains positively charged amino acids and is highly conserved domain while subdomain D has ability to bind the DNA(16,18). According to a report,15 variants (A-O) of NAC protein have been identified in rice that are different in their structures based on their amino acid domains(19).Type A - E contains five motifs that are present in standard NACDNA binding domain, and type F - O consists of a distinct motif conformation in ' NAC-like ' proteins. Due to structural variationsin various motifs, these proteins shows possibly diverse functions and have unidentified specificities.

X-ray crystal structure:

After studying crystallography and insilico investigation inSetariaitalicaSiNAC, Arabidopsis thalianaAtNAC019 and in Oryza sativastress-responsive NAC1 (SNAC1) proteins, it is revealed thatthese transcription factorsare comprised of a twisted b-sheets (b1-6/7) that are antiparallel, used for DNA binding and positioned between an N-extreme of alpha turn and a short helix (18,20).Amino acid composition of DB domain reveal that 19 to Serine183, b4 to 6 zone D – E, Lysine123 and Lysine126, b4–5 zone D and Lysine79, Arginine85 and Arginine88, b1–2 zone C (13,18).In DNA binding affinities, Lysine79 and Arginine85 are distinct so that they are exchangeable residues whereas Arginine is 88 is retained in all NACproteins (16).

In fact, the protein binding action of NAC transcription factorsregulates the fate and role of the NAC protein(13,24).These interactions are important between plants and pathogens as well as in stress tolerance (21).The D subunit is extremely hydrophobic negative regulatory domain (NRD) in some NAC proteins, which limits transcriptional activity [Fig 1 (ii)]. Even other TF families such as DNA-binding with one finger(Dof), WRKY and AP2/DRE can be suppressed by the NRD-like sequences(8).

NACtranscription regulatory regions (TRRs):

Structural analysis reveal that transcription regulatory regions (TRRs)are usually located at C-terminal(Figure 1 (i)). These regions can stimulate(22)or suppressthe rate of transcription of various genes (23,24). The Transcriptional regulatory regions haveconserved amino acid sequences that are abundant in Ser-Thr, Pro-Glu repeats or acidic amino acids.It is identified that ten TRR regions are present in NAC proteins in rice(19).It has shownthat these regions are similar for subgroups ofNAC subdivision but there is variation across different subdivision(14). Thus, TTRs showsmodifications according to specificroles of NAC proteins in different plants. Due to the less complicated sequences, transcription regulatory regioncontains a high level of intrinsic dysfunction (ID) and it does not contain any stable 3D structure (16,25). This flexibilityfacilitates the formation of model proteins by interacting them with different target proteins for structural and TF functional analysis.The TTR’s of some NAC proteins have the ability to bind several proteins with it (25). The pattern of alpha-helical trans membrane (TM) found in some NAC proteins (named NTLs) is responsible for anchoring the cell membrane or ER membrane(Fig 1(ii)) (26).

NAC function and Expression:

NAC transcription factorshave rolein a number of processes, including plant development(13), secondary wall synthesis (27) maturity (25,28), biotic (13,29)and abiotic stresses(30,31).The genome-wide transcriptomestudyand bioinformatics study shows 20 to 25 percent of NAC genes working at least in one stress response or another (19,32).

NAC regulation and activity:

Transcriptional regulation:

Transcription factors have role in regulation level of transcription(Figure 2). Studies of leaf to protoplastic evolution indicated that multi-potential advances includes triggering multiple silent NAC genes (33,34). Other example is the NACnrp1, endosperm, controlled by genomic imprinting.Patrilineal transferred alleles are therefore suppressed, permitting maternal regulation of the production of endosperm(35).

Post-transcriptional regulation:

miRNAs are small RNAs with a regulatory association to the targeted mRNAs which allow the targets to be repressed after transcription (36). Computer analysis shows that transcription factors implicated in the determination of cell-fate are the primary objectives of miRNAs in plants(37). Initially, a subclass of ArabidopsisNAC mRNAs including CUC1, CUC2, Nac1, 5g07680 mRNA’s and CUC1 and CUC2 were estimated as a targeting component of the miR164 gene family, and their additional miR164 sites were blocked (38). However, the miR164 expression resistant for CUC1 and CUC2 mRNA’s and miR164 overexpression showed that miR164 is compulsory in order to regulate the CUC1 and CUC2 correctly. miR164-directed NAC1, At5g07680 and At5g61430 were identified by representing the significance of post-transcription regulation of different NAC genes (39, 40). Another regulation pointat the RNA level is the long term phloem transference of the NAC mRNA CmNACP in Cucurbita maxima. A pathway that integrates physiological processing in the distant organs with development in meristematic tissue, CmNACPmRNA is shifted from plant body to shooting apex(41) (Figure 2).

Post-translational regulation:

Post translation regulation by ubiquitine-mediated protein degradation is also used to control the NAC activity (42). The degradation of proteins is targeted by the polyubiquitation of the proteins E1, E2 and E3 by sequential action (43). SINAT5 (Arabidopsis thaliana 5 SINA) was established as an interaction partner of NAC1 with a yeast 2 hybrid screening (42). SINAT5 has been demonstrated to act as an E3 protein ligase and targeted for NAC1 in order to degrade proteasomes (Figure 2).

NAC function in Abiotic stress:

During stress response in plants, the NAC TF’s acts as an important component of varioussignaling pathways. Various plants havemoderatelya huge range of NAC transcription factors and shows their diverse and unknown functionsunder variousenvironmental stimuli, and finding their role in abiotic stress is considered a major challenge. In recent studies, NAC protein may have been indirectly involved in abiotic stresses from transcription modeling and functional studies. In general, the facts presented here summarizes the role of various NAC transcription factors in controlling transcriptional reprogramming to plant’s abiotic stresses (Fig. 3, Table 1).

During plant stress response,NAC proteins act as an important component in the diverse signaling pathways. Various plants have relatively large numbers of NAC transcription factors and their diverse and unknown roles in complex environmental stimuli and finding their role in abiotic stress is considered as big challenge. The strict modulation of NAC in plant stress conditions participate in the development of diverse signaling networks and prospective candidates for stress tolerance are the significant function of NAC for herbal abiotic stress responses.

Abiotic stresses causeawidespread range of reaction in plants, from changes in the expression of gene and cell metabolism to modifications in plant progress, reproduction and yield performance. Desiccation and NaCl sensitivity in transgenic Oryza Sativa has been increased after overexpression ofOs01g66120/OsNAC2/6 and Os11g03300/OsNAC-10 (44, 45). It has also reported that overexpression of Os03G60080/SNAC1resulted in improvement of plant growth from 21 to 34 % under low water availability (4). Comparativeexpression studiesof genes has been identified as an effective method to recognize stress response pathways and genes under different stress conditions (46). A complete relationshiphas been identified in the Arabidopsis NAC gene ANAC092 (47), during seed maturation and salt-promoting senescence.Various studies revealed that a significant part of dehydration-regulated genes are also fertilization-regulated; pollen is still the main spot of variability in rates of expression among various genes (48, 49).Subsequent studies focused on the GUS-promoter fusions for rice and Arabidopsis of cold inducinggenes (Os01g66120/SNAC2/6, Os11g03300/OsNAC10 and RD29A, COR15A and COR6.6) were found to upregulated under both stressed and under stressedconditionsand during the plant growth (45, 50). OsOAT is a target gene of NAC stressinducing transcription factor. SNAC2and OsOAT overexpression in Oryza Sativa has contributed to a significantly increased during drought and osmotic stress conditions (51). Plants that over-express GmNAC085 show increased tolerance to drought (7) whileGmNAC11 overexpression has directed to increaseNaCl and mannitol stress tolrenace (8). The activation of 17 NAC genes under low water potential has been reported by microarray analysis in rice roots(52).Over expression of SiNACfrom foxtail millet has also resulted duringvarious stresses including drought, high salt concentration, and methyl jasmonate(20). Transgenic Tobacco (Nicotianatabacum) transformed with various NAC genes including DgNAC1, TaNAC2a and EcNAC1isolated from bacteria and higher plants showed tolerance to salinity and drought conditions (53, 54, 55).

NAC role in biotic stress:

A number of studies regarding NAC transcriptionfactor show the significance of various members of the multigene family in the transcriptional reprogramming of the plant immunized response.The research has been reviewed extensively and will therefore be briefly examined here.Apparently, the NAC TF’s are the main elements of different characteristics in the innate immune system, essential defense and complete resistance of a crop. This is an important field of research that has been thoroughly examined and is thus only mentioned shortly here. Apparently, NAC TF’s are essential components for many aspects of the endogenous, fundamental and systemic immune system in plants.

There are several cases of overexpression or low NAC gene expression influencing plant defence, which have enabled some components of the signal pathway to be resolved(Figures 3,4; Table 2) (16, 56, 57). In order to assess the function of NAC transcription factors (ONAC122 and ONAC131) in M. grisea resistance disease, Sun andco-workers used VIGS systems (58). Virus-induced gene silencing is a valuable tool for fast genetic feature investigation in plants (59, 60). Virus-induced gene silencing have been established for dicot species, in which the tobacco virus based VIGS vector for Solanum, tobacco and the tomatois a most successful model (61). The VIGS vector of barley stripe mosaic virus is used to elucidate the role of several genes in wheat and barley disease resistance (50). Researchers have created a brome mosaic vector based VIGS, which has been shown to be a powerful method to rapidly evaluate the gene function of barley, rice and maize (62, 63). In germinating rice seedlings 19 and 13 genes have been upreglatedafter RSV and RTSV inflamations at several daysinoculations, respectively (32). Many NAC proteins have been shown to over expressed as a result of attacks by viruses, various fungal elicitor and bacteria that may bothincrease or decrease the viralgrowth by interacting with virus-encrypted proteins and increase in NAC expression levels (9,64,65,66). The interaction of NAC proteins with different regulatory network is a consequence of this dual regulation in plant defense. OsNAC4 is the main positive regulator for hypersensitive plant cell death, with dramatically declining hypersensitive cell mortality as a consequence of non-infectious bacterial strains on OsNAC4 knock-down line. OsNAC4 will be transferred to the nucleus according to the phosphorylation after inducingavirulent pathogens perceiving signal. On the other side, the OsNAC6 overexpression does not result in hypersensitive cell mortality (67), whileOsNAC6 over-sensitive Oryza sativa plants has the ability to tolerate blast disease (68). An increased sensitivity of ATAF2 overexpression against the parasitic infection Fusariumoxysporum during proper situations due to pathogenesis associated suppression (69), which contributed to an enhanced vulnerability for pathogenesis-related (PR) genes caused to the non-sterile aggregation of tobacco mosaic viruses (66).The role of NAC transcription factors in several plant-patent association has also been identified in RNA interference and overexpression analysis (67, 70). The role ofATAF1 and its Barley Homolog HvNAC6 has also been shown to positively control penetration susceptibility to Blumeriagraminisf.sp. biotrophic fungus RNA studies and over-expression findings. The aim is to reduce resistance forvarious diseases, including Bacterial, and fungal diseases (56, 57). In comparison to ATAF2, transcription-activators are ATAF1 and HvNAC6 and can potentially control PR repression through imaginary negative regulators. Therefore, it seems that the ATAF subfamily has a retained but not obsolete role in regulating reactions to different pathogenic agents. The immune reaction in pathogen-borne plant species is defined by several defensive responses that are controlled by the various types of TF such as the production of the significant number of resistance associated genes (71).Arabidopsis NAC genes that are stress-responsive, including RD26 relate to JA, a well-known phytohormone that works to improve plant damage (3, 72).

Prospects for future research:

After the identification of the NAC transcription factor family the study of the physiological and molecular roles of NAC protiens was extended further. However, it is still the beginning of this area of research. The occurrenceof broad NAC gene families in an extensivevariety of plants represents a challanging task in assessing the roles of NAC.

In addition, NAC work would definitely benefit from specific functional review approaches.It is of huge attention to identify targeted NAC genes. One important technique is the overexpression of NAC genes in association with microarray investigation. The TF binding sites of genomic DNA are shown by microarrays in combination with chromatin immunoprecipitation (73). Many knockout mutants are likely to be helpful due to their functional stability. Alternatively, RNA silencing (35) and chimeric repressor silencing (3, 74) could also be used. In functional genomics, further analysis of the molecular roles of these transcription factors is important for a better function of NAC protein.

This will also include a detailed examination of NAC protein interactions with DNA and other proteins. In addition to TCP transcription factors, viral proteins and RING proteins, the study of protein-protein interactions can provide important information on plant defense mechanisms, controlled protein degradation and plant growth. In addition, consideration should be given to the association of the regulated NAC protein regions with the transcriptional mechanism. The relationship between NAC protein and TCP transcription factors and its ability to dimerize homo and hetro indicates a combinatorial modulation of transcription factor activity (75). So it is obviousthat NAC proteins functions with other transcription factors at both upstream and downstream regions. Therefore, a major aim of research on NAC proteins is to brighten up theirrole in networks of transcription factor.

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Table 1: NAC TF’s families involved in abiotic stress-responsive pathways in plants:

Table 2: Role of NAC transcription factors in stress response

Fig 1.Structure and regulation of NAC proteins: Diagrammatic description demonstrate (i) a standard NAC protein at the N-region with aextremely conserved NAC motif that is sub-divided into five conserved subdomains (A – E).This zone containsDNA binding ability that follows protein binding and dimerization. C-terminal is diverse and supports an activator or repressor-functional transcriptional regulatory (TR) dominant domain which may often carry protein binding activity. (ii)In various circumstances a trans membrane motif (TM) in the C-terminal is found in the NAC domain and a blue shaded negative control domain. Changes in standard NAC proteins contain those programming(iii) the NAC motifs, (iv) two tandemly repeated NAC motif, (v) a N-terminal extendedarea (NTR) moving towards NAC domain (vi) Vascular plant One-Zinc fingerproteins (VOZ), where the NAC region is located at the C terminal and the TR region is located at the N-end with a zinc finger motif (ZF) working as a conserved DNA binding domain.

Figure 2. Regulation and location of NAC protien. The regulatory pathway shows the affect of levels of NAC proteins or the position of the protein are described at right side, with the arrows showing the level of DNA, mRNA or protein regulation. Abbreviation: NES (nuclear export signal), HSINAC(HvSPY-interacting NAC), NLS (nuclear localization signal).

Box 1. Regulation of nuclear localization:

Fig 3. The function of NAC TF’s in the signaling pathway for herbivores / biotic and abiotic.

FIGURE 4. Factors of NAC transcription are key components of gene expression transcriptional regulation in viral diseases. Abbreviations: WDV (wheat dwarf geminivirus), TCV (turnip crinkle virus); TIP (TCV-interacting protein). TLCV (tomato leaf curl virus), TMV (tobacco mosaic virus).