Fto Synthesis

Improved Essays
FTO belongs to a member of Fe(II)- and α-ketoglutarate-dependent AlkB dioxygenase family and was originally recognized as an enzyme involved in the excision of N1- or N3-modified purine or primidine in both DNA and RNA substrates. Jia et al. for the first time demonstrated that human FTO could also demethylate m6A on nuclear RNAs in vitro, and increase and decrease in m6A was manifested in FTO-depleted and overexpressed-HeLa cell, respectively. FTO function has shown to link to the regulation of body fat homeostasis in human. Consistent with the notion, a study reported that FTO regulates alternative splicing of RUNX1T1, an adipogenic factor, by removing m6As, which are located around splicing junctions. Fto knockout (KO) animal exhibited …show more content…
Although multiple AlkB homologue genes have been identified in mammalian genome, their function and substrates have been elusive. Zheng et al. demonstrated that human ALKBH5 protein efficiently catalyzes demethylation of m6A containing RNAs. Utilization of iron by ALKBH5 protein during catalytic reaction seems to be critical as mutant version (H206A or H266A) of iron center in ALKBH5 protein compromised its demethylation activity. Furthermore, the depletion of ALKBH5 increased the m6A level and accumulated poly[A]-tailed RNA in cytoplasm, causing sterility in male KO …show more content…
As discussed, recent studies highlighted some m6A functions in ESCs and developmental processes. However, there are many remaining questions regarding m6A function in ESC biology. For instances, there are lack of evidences demonstrating definitive functions of both m6A by itself and related enzymes in adult stem cells such as hematopoietic stem cells and intestinal stem cells. In addition, the role of each m6A-modifying enzyme in tissue-specific manner is not investiagted. One way to prove their functions is to use conditional KO strategies as conventional KO of some of enzymes, leading to embryonic lethality. A shift of transcriptome (from maternal transcripts to zygotic transcripts: known as maternal-to-zygotic transition (MZT)) is known to occur during mammalian preimplantation development. A recent study showed that Xenopus oocyte mRNA methylation can regulate translation and cell division during meiosis and early embryo development. Therefore, m6A may possibly play a role in the process of MZT. Finally, the involvement of m6A in onset or progress of human diseases is still elusive. The possibility of this phenomenon in patient derived tissues should be proved in the near future based on experimental

Related Documents

  • Superior Essays

    1998). To model this exon-skipping event, I will generate a targeting construct that will place the loxP sites on the introns flanking exon 10 and exon11 upon homologous recombination in ES cells. To control the expression of the floxed Upf1 allele, I will place a lox-stop-lox cassette in the first intron of Upf1 that causes transcription termination in the absence of Cre-recombinase. To restrict expression of Upf1 mutants to the pancreas, I will cross the Upf1 floxed mice with PDX1-CRE expressing mice(Hingorani, Petricoin et al. 2003).…

    • 1047 Words
    • 4 Pages
    Superior Essays
  • Improved Essays

    In the nucleus, Smads are also able to participate in histone modifications and chromatin remodeling (Ross et al., 2006 [53]). Anyway, some transcription factors like Runx1, Runx2, and Runx3 in concert with R-Smads and/or Smad complex plays critical roles in mediating specific signals to regulate the transcription of ultimate target genes. Essentially, Runx2 regulate osteoblasts formation and activate the expression of other osteogenesis specific target genes. The β subunit of PEBP2 stabilizes Runx2 by preventing ubiquitin-dependent degradation (James, 2013 [54]). Upon activation of BMP…

    • 931 Words
    • 4 Pages
    Improved Essays
  • Improved Essays

    Folliculin Case Study

    • 884 Words
    • 4 Pages

    This will be biochemically analyzed through co-immunoprecipitation of HEK293T cells stably expressing FLAG-RagB who are starved from 50mins and then re-stimulated with glutamine for 10mins and immunoblot for endogenous FLCN levels. If FLCN is glutamine sensitive, you should see a transition from protein interaction between FLCN and RagB seen under…

    • 884 Words
    • 4 Pages
    Improved Essays
  • Superior Essays

    Gene Trap Essay

    • 1765 Words
    • 8 Pages

    i. The concern of gene trapping bias against developmental process later stage. Mouse ES gene trapping technology depends on mouse ES cells for screening gene trapping mutations, the genes of interest have to be expressed in mouse ES cells in order for them to be trapped. It is seen that the developmental regulators in embryonic stage has been effectively mutated but the efficiency in adult stage is not very clear. ii.…

    • 1765 Words
    • 8 Pages
    Superior Essays
  • Great Essays

    Does FLCN require FNIP to sense amino acids? Folliculin exists in a complex by binding to either of its novel interacting proteins, FNIP1 or FNIP2. Truncation mutations commonly seen in FLCN gene of BHD patients promote the loss of binding with FNIPs (). Moreover, FLCN must exists as a complex to interact with the Rag GTPases because individual purified protein components abolish FLCN-FNIP interactions with RagA/C (Tsun). Further biochemical evidence discovered FLCN-FNIP GAP activity can only occur as a complex because when expressed individually potentiates its GTP hydrolysis function (Tsun).…

    • 1931 Words
    • 8 Pages
    Great Essays
  • Superior Essays

    Genet., 13 (2), 145–153. 14. Beutler, E., Kuhl, W., Trinidad, F., Teplitz, R., and Nadler, H. (1971) Beta-glucosidase activity in fibroblasts from homozygotes and heterozygotes for Gaucher’s disease. Am. J. Hum.…

    • 2123 Words
    • 9 Pages
    Superior Essays
  • Improved Essays

    The study conducted by Yang et al. shows that CHIP regulates the level of katanin-p60 protein, which is required for the proper axonal growth in early developmental stages. CHIP antagonizes the effects of a deubiquitylating enzyme, USP47 by ubiquitinating and destabilizing katanin-p60 and hence presents an important role in axonal growth (Yang et al., 2013). Another study showed abnormal motor disturbances with altered phenotypic and behavioral functions in CHIP heterozygous mice (McLaughlin et al., 2012). CHIP may also have some indirect regulatory roles over various neurodevelopmental processes through its large number of substrates, where it regulates various proteins which are directly involved in brain development processes.…

    • 1627 Words
    • 7 Pages
    Improved Essays
  • Superior Essays

    Oxysterol Essay

    • 1503 Words
    • 7 Pages

    The modulation of cholesterol metabolism may be mediated through transcription factors. Accordingly, ORP8 was shown to regulate activity of SREBP, presumably by an indirect mechanism (Zhou et al., 2011). ORP2 binds LXRs and is required for expression of LXR target genes (Escajadillo et al., 2016). OSBP family modulates also vesicular transport. OSBP1 interacts with VAP-A protein, which is important for protein and lipid transport to the Golgi apparatus (Wyles et al., 2002).…

    • 1503 Words
    • 7 Pages
    Superior Essays
  • Improved Essays

    Eukaryotic Synthesis

    • 1359 Words
    • 6 Pages

    As described in the central dogma of biology, information from a gene can be used to build a protein in a two-step process. Transcription is considered to be the first step of gene expression. It is known to be the process of making a copy of genetic information stored in a DNA strand into a complementary strand of messenger RNA (mRNA). The process of eukaryotic transcription can be separated into three phases, initiation, elongation and termination. This complex process involves various cell signaling methods as well as the activity of many enzymes.…

    • 1359 Words
    • 6 Pages
    Improved Essays
  • Improved Essays

    Apoptosis Research Paper

    • 773 Words
    • 4 Pages

    To begin, a protein kinase inhibitory drug, staurosporine, can induce apoptosis in mammalian cells and it can also induce like features in L. major. This draws an important connection between unicellular eukaryotes and mammalian cells because multicellularity emerged after unicellular eukaryotes thus this means that the multicellular eukaryotes must have inherited their apoptosis functions from their unicellular eukaryotic ancestors. Some features of the programmed cell death that are expressed by L. major cells during the process is cell shrinkage, phosphatidyl serine exposure on the cell surface, mitochondrial transmembrane potential disruption and the degradation of the cell’s DNA. Other drugs — UV treatment, heat shock, etc.— that typically induce apoptosis in mammalian cells can also get similar results from L. major. This goes…

    • 773 Words
    • 4 Pages
    Improved Essays