Browsing by Author "Zhang, Fangyuan (TTU)"
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Item A Multi-Parameter Analysis of Cellular Coordination of Major Transcriptome Regulation Mechanisms(2018) Jiang, Wen (TTU); Guo, Zhanyong; Lages, Nuno; Zheng, W. Jim; Feliers, Denis; Zhang, Fangyuan (TTU); Wang, Degeng (TTU)To understand cellular coordination of multiple transcriptome regulation mechanisms, we simultaneously measured transcription rate (TR), mRNA abundance (RA) and translation activity (TA). This revealed multiple insights. First, the three parameters displayed systematic statistical differences. Sequentially more genes exhibited extreme (low or high) expression values from TR to RA, and then to TA; that is, cellular coordination of multiple transcriptome regulatory mechanisms leads to sequentially enhanced gene expression selectivity as the genetic information flow from the genome to the proteome. Second, contribution of the stabilization-by-translation regulatory mechanism to the cellular coordination process was assessed. The data enabled an estimation of mRNA stability, revealing a moderate but significant positive correlation between mRNA stability and translation activity. Third, the proportion of mRNA occupied by un-translated regions (UTR) exhibited a negative relationship with the level of this correlation, and was thus a major determinant of the mode of regulation of the mRNA. High-UTR-proportion mRNAs tend to defy the stabilization-by-translation regulatory mechanism, staying out of the polysome but remaining stable; mRNAs with little UTRs largely followed this regulation. In summary, we quantitatively delineated the relationship among multiple transcriptome regulation parameters, i.e., cellular coordination of corresponding regulatory mechanisms.Item AIJ: Joint test for simultaneous detection of imprinting and non-imprinting allelic expression imbalance(2020) Chen, Dao Peng; Zhang, Fangyuan (TTU); Lin, ShiliEpigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence. Genomic imprinting is an epigenetically regulated process by which imprinted genes are expressed in a parent-of-origin-specific manner. It can be confounded with a phenomenon, allelic expression imbalance (AEI), which, in this paper, refers to asymmetric expression of the two alleles of a heterozygous subject at a single nucleotide polymorphism not caused by imprinting (non-imprinting AEI). Since existing methods in the literature are not amenable to distinguishing imprinting from non-imprinting AEI for data without replicates, we propose AIJ, a joint test for simultaneous detection of imprinting and non-imprinting AEI that accounts for potential confounding using RNA-seq data based on a reciprocal cross design. Through a simulation study, we show that AIJ is more powerful compared to two frequently used methods that do not account for confounding. To illustrate the practical utility of AIJ, we applied the method to a mouse dataset and identified genes with the imprinting effect and/or non-imprinting AEI phenomenon, with some already confirmed in an existing database. The results are also largely consistent with a study on human data for a set of orthologous genes, affirming earlier conclusion in the literature that non-imprinting AEI events are evolutionarily conserved.Item Comparative Analysis of microRNA Binding Site Distribution and microRNA-Mediated Gene Expression Repression of Oncogenes and Tumor Suppressor Genes(2022) Shuangmei, Tian (TTU); Wang, Jing; Zhang, Fangyuan (TTU); Wang, Degeng (TTU)MicroRNAs (miRNAs) are a family of short, noncoding RNAs that can regulate gene expression levels of over half of the human genome. Previous studies on the role of miRNAs in cancer showed overall widespread downregulation of miRNAs as a hallmark of human cancer, though individual miRNAs can be both tumor suppressive and oncogenic, and cancer genes are speculated to be more targeted by miRNA. However, the extents to which oncogenes and tumor suppressor genes (TSG) are controlled by miRNA have not been compared. To achieve this goal, we constructed lists of oncogenes and TSGs and compared them with each other, and with the whole protein-coding gene population, in terms of miRNA binding sites distribution and expression level changes upon genetic disruption of miRNA production. As expected, the results show that cancer gene mRNAs anchor more miRNA binding sites, and are under a higher degree of miRNA-mediated repression at both mRNA abundance and translation efficiency levels than the whole protein-coding gene population. Importantly, on average, TSG mRNAs are more highly targeted and regulated by miRNA than oncogene mRNAs. To the best of our knowledge, this is the first comparison of miRNA regulation of oncogenes and TSGsItem Effects of irrigation rates on cotton yield as affected by soil physical properties and topography in the southern high plains(2021) Neupane, Jasmine (TTU); Guo, Wenxuan (TTU); West, Charles P. (TTU); Zhang, Fangyuan (TTU); Lin, Zhe (TTU)Lack of precipitation and groundwater for irrigation limits crop production in semi-arid regions, such as the Southern High Plains (SHP). Advanced technologies, such as variable rate irrigation (VRI), can conserve water and improve water use efficiency for sustainable agriculture. However, the adoption of VRI is hindered by the lack of on-farm research focusing on the feasibility of VRI. The objective of this study was to assess the effect of irrigation rates on cotton yield as affected by soil physical properties and topography in the Southern High Plains. This study was conducted in two fields within a 194-ha commercially managed farm in Hale County, Texas, in 2017. An irrigation treatment with three rates was implemented in a randomized complete block design with two replications as separate blocks in each field. A total of 230 composite soil samples were collected from the farm in spring 2017 and analyzed for texture. Information on apparent soil electrical conductivity (ECa), elevation, and final yield were collected from the fields. A statistical model showed that the effect of irrigation rates on cotton yield depended on its interaction with soil physical properties and topography. For example, areas with slope >2% and sand content >50% had no significant response to higher irrigation rates. This model suggests that applying irrigation amounts based on the yield response can be a basis for VRI. This study provides valuable information for site-specific irrigation to optimize crop production in fields with significant variability in soil physical properties and topography.Item The Enrichment of miRNA-Targeted mRNAs in Translationally Less Active over More Active Polysomes(2023) Wang, Tingzeng (TTU); Tian, Shuangmei (TTU); Tikhonova, Elena B. (TTUHSC); Karamyshev, Andrey L. (TTUHSC); Wang, Jing J.; Zhang, Fangyuan (TTU); Wang, Degeng (TTU)miRNAs moderately inhibit the translation and enhance the degradation of their target mRNAs via cognate binding sites located predominantly in the 3′-untranslated regions (UTR). Paradoxically, miRNA targets are also polysome-associated. We studied the polysome association by the comparative translationally less-active light- and more-active heavy-polysome profiling of a wild type (WT) human cell line and its isogenic mutant (MT) with a disrupted DICER1 gene and, thus, mature miRNA production. As expected, the open reading frame (ORF) length is a major determinant of light- to heavy-polysome mRNA abundance ratios, but is rendered less powerful in WT than in MT cells by miRNA-regulatory activities. We also observed that miRNAs tend to target mRNAs with longer ORFs, and that adjusting the mRNA abundance ratio with the ORF length improves its correlation with the 3′-UTR miRNA-binding-site count. In WT cells, miRNA-targeted mRNAs exhibit higher abundance in light relative to heavy polysomes, i.e., light-polysome enrichment. In MT cells, the DICER1 disruption not only significantly abrogated the light-polysome enrichment, but also narrowed the mRNA abundance ratio value range. Additionally, the abrogation of the enrichment due to the DICER1 gene disruption, i.e., the decreases of the ORF-length-adjusted mRNA abundance ratio from WT to MT cells, exhibits a nearly perfect linear correlation with the 3′-UTR binding-site count. Transcription factors and protein kinases are the top two most enriched mRNA groups. Taken together, the results provide evidence for the light-polysome enrichment of miRNA-targeted mRNAs to reconcile polysome association and moderate translation inhibition, and that ORF length is an important, though currently under-appreciated, transcriptome regulation parameter.Item The pattern of microRNA binding site distribution(2017) Zhang, Fangyuan (TTU); Wang, Degeng (TTU)Micro-RNA (miRNA or miR) regulates at least 60% of the genes in the human genome through their target sites at mRNA 3’-untranslated regions (UTR), and defects in miRNA expression regulation and target sites are frequently observed in cancers. We report here a systematic analysis of the distribution of miRNA target sites. Using the evolutionarily conserved miRNA binding sites in the TargetScan database (release 7.1), we constructed a miRNA co-regulation network by connecting genes sharing common miRNA target sites. The network possesses characteristics of the ubiquitous small-world network. Non-hub genes in the network—those sharing miRNA target sites with small numbers of genes—tend to form small cliques with their neighboring genes, while hub genes exhibit high levels of promiscuousness in their neighboring genes. Additionally, miRNA target site distribution is extremely uneven. Among the miRNAs, the distribution concentrates on a small number of miRNAs, in that their target sites occur in an extraordinarily large number of genes, that is, they have large numbers of target genes. The distribution across the genes follows a similar pattern; the mRNAs of a small proportion of the genes contain extraordinarily large numbers of miRNA binding sites. Quantitatively, the patterns fit into the P(K) ∝ K−α relationship (P(K): the number of miRNAs with K target genes or genes with K miRNA sites; α: a positive constant), the mathematical description of connection distribution among the nodes and a defining characteristic of the so-called scale-free networks—a subset of small-world networks. Notably, well-known tumor-suppressive miRNAs (Let-7, miR-15/16, 26, 29, 31, 34, 145, 200, 203–205, 223, and 375) collectively have more than expected target genes, and well-known cancer genes contain more than expected miRNA binding sites. In summary, miRNA target site distribution exhibits characteristics of the small-world network. The potential to use this pattern to better understand miRNA function and their oncological roles is discussed.Item Uncovering the cellular capacity for intensive and specific feedback self-control of the argonautes and MicroRNA targeting activity(2020) Wang, Degeng; Wang, Tingzeng; Gill, Audrey (TTU); Hilliard, Terrell; Chen, Fengqian; Karamyshev, Andrey L. (TTUHSC); Zhang, Fangyuan (TTU)The miRNA pathway has three segments - biogenesis, targeting and downstream regulatory effectors. We aimed to better understand their cellular control by exploring the miRNA-mRNA-targeting relationships. We first used human evolutionarily conserved sites. Strikingly, AGOs 1-3 are all among the top 14 mRNAs with the highest miRNA site counts, along with ANKRD52, the phosphatase regulatory subunit of the recently identified AGO phosphorylation cycle; and the AGO phosphorylation cycle mRNAs share much more than expected miRNA sites. The mRNAs for TNRC6, which acts with AGOs to channel miRNA-mediated regulatory actions onto specific mRNAs, are also heavily miRNA-targeted. In contrast, upstream miRNA biogenesis mRNAs are not, and neither are downstream regulatory effectors. In short, binding site enrichment in miRNA targeting machinery mRNAs, but neither upstream biogenesis nor downstream effector mRNAs, was observed, endowing a cellular capacity for intensive and specific feedback control of the targeting activity. The pattern was confirmed with experimentally determined miRNA-mRNA target relationships. Moreover, genetic experiments demonstrated cellular utilization of this capacity. Thus, we uncovered a capacity for intensive, and specific, feedback-regulation of miRNA targeting activity directly by miRNAs themselves, i.e. segment-specific feedback auto-regulation of miRNA pathway, complementing miRNAs pairing with transcription factors to form hybrid feedback-loop.