Archives

  • 2018-07
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • As mentioned earlier two different isoforms

    2022-08-05

    As mentioned earlier two different isoforms of TFE3 [16] have been reported viz. the full length (TFE3L) and smaller (TFE3S) without exon 1&2. TFE3S lacks an N-terminal acidic activation domain which is present in TFE3L hence is a dominant negative form of TFE3L [51]. This dominant negative feature is also associated with a TFE3 fusion protein PRCC-TFE3 [52], [53]. Since the functional phenotype of the alternative splicing and the translocation of TFE3 is similar, G-quadruplex role in translocation and splicing was studied. Studies have shown that G-quadruplexes are involved in the alternative splicing, displaying their role in enrichment of a particular form which might be pathogenic. In minigene based model we studied the role of G-quadruplex in TFE3 splicing and after PDS treatment level of different isoforms changes displaying G-quadruplex role in TFE3 splicing. Our study investigated the formation of a stable G-quadruplex structure from TFE3 intron 2 PQS and its role in TFE3 alternative splicing and translocation.
    Funding
    Conflict of interest
    Transparency document
    Acknowledgement
    Single-stranded DNAs containing a repeating sequence of nucleobases can form alternative secondary structures through non-canonical OPP receptor pairs. The most well-studied and highly characterized secondary structure in the past two decades is the G-quadruplex DNA, which is known to be formed by guanine-rich DNA sequences. The basic structural unit of G-quadruplex is the G-quartet, which is derived from the association of four guanines into a cyclic Hoogsteen hydrogen bonding arrangement , , , . Studies revealed that putative G-quadruplex-forming DNA sequences are highly prevalent in human genes, especially in telomere structures at the ends of chromosomes and in promoter regions of some oncogenes . It is believed that G-quadruplex DNA structures play a significant regulatory role in many biological processes, such as transcriptional regulation, DNA replication, telomere maintenance and antitumor chemotherapy . The ever-increasing interest in the area of the G-quadruplex requires the development of selective G-quadruplex-targeting probes to improve our understanding of G-quadruplexes and their binding characteristics . Thiazole orange () is an exceptional asymmetric cyanine dye. It possesses many distinctive and desirable properties: low intrinsic fluorescence emission, chemical stabilities, and a high molar absorption coefficient. Moreover, has a high binding affinity to double-stranded DNA with intense fluorescence enhancement . These unique properties make particularly useful for the detection of double-stranded nucleic acids in a variety of techniques. In addition to duplex DNA, can also stack on G-quartet and has been reported for the detection of G-quadruplex DNAs . The common problems like non-selective for G-quadruplex and emission in the lower wavelength region of spectrum (green region), hamper its further applications. In fact, probes with absorption in the longer wavelength of the visible region and emission in the far-red region (600–750 nm) are highly sought-after due to minimal auto-fluorescence and cellular damage . These limitations need to be considered while designing new molecular probes. Several research groups have undertaken the challenging task of chemical modification of in order to enhance its binding affinity and selectivity and push its emission wavelength into the far-red region . Based on our previous experience in designing selective G-quadruplex DNA fluorescent probes, we found that a flexible amine chain of the structure core was observed to be better in the terms of selectivity and binding affinity toward G-quadruplex DNA . Herein, we attempted to design far-red fluorescent probes ( and ) by introducing flexible amine side groups to the template (), aiming to optimize the selectivity for G-quadruplex DNA and photophysical property. Their photophysical characterization and fluorescence performance on G-quadruplex DNA were investigated. with a shorter amine chain gives a better selectivity for G-quadruplex DNA with far-red emitting. The detailed binding affinity and mechanism for G-quadruplex DNA was assessed by UV–vis spectrophotometry, fluorescence, circular dichroism, FID assay and KI quenching experiment. In addition, the binding mode of was also studied by computational methods.