scholarly journals Two separation-of-function isoforms of human TPP1 and a novel intragenic noncoding RNA dictate telomerase regulation in somatic and germ cells

2019 ◽  
Author(s):  
Sherilyn Grill ◽  
Kamlesh Bisht ◽  
Valerie M. Tesmer ◽  
Christopher J. Sifuentes ◽  
Jayakrishnan Nandakumar

SummaryTelomerase replicates chromosome ends in germ and somatic stem cells to facilitate continued proliferation. Telomerase action depends on the telomeric protein TPP1, which recruits telomerase to telomeres and facilitates processive DNA synthesis. Here we identify separation-of-function long (TPP1-L) and short (TPP1-S) isoforms of TPP1 differing only in 86 amino acids at their N-terminus. While both isoforms retain the ability to recruit telomerase, only TPP1-S facilitates telomere synthesis. We identify a novel intragenic noncoding RNA in the 3’-UTR of the TPP1-encoding gene that specifically shuts down telomerase activation-incompatible TPP1-L to establish TPP1-S as the predominant isoform in somatic cells. Strikingly, TPP1-L is the major isoform in testes, where it can function to restrain telomerase in mature germ cells. Our studies uncover how differential expression of two isoforms allows TPP1 to perform separate functions in different cells, and demonstrate how isoform choice can be determined by an intragenic noncoding RNA.

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Irma Virant-Klun ◽  
Anders Ståhlberg ◽  
Mikael Kubista ◽  
Thomas Skutella

MicroRNAs are a family of naturally occurring small noncoding RNA molecules that play an important regulatory role in gene expression. They are suggested to regulate a large proportion of protein encoding genes by mediating the translational suppression and posttranscriptional control of gene expression. Recent findings show that microRNAs are emerging as important regulators of cellular differentiation and dedifferentiation, and are deeply involved in developmental processes including human preimplantation development. They keep a balance between pluripotency and differentiation in the embryo and embryonic stem cells. Moreover, it became evident that dysregulation of microRNA expression may play a fundamental role in progression and dissemination of different cancers including ovarian cancer. The interest is still increased by the discovery of exosomes, that is, cell-derived vesicles, which can carry different proteins but also microRNAs between different cells and are involved in cell-to-cell communication. MicroRNAs, together with exosomes, have a great potential to be used for prognosis, therapy, and biomarkers of different diseases including infertility. The aim of this review paper is to summarize the existent knowledge on microRNAs related to female fertility and cancer: from primordial germ cells and ovarian function, germinal stem cells, oocytes, and embryos to embryonic stem cells.


2008 ◽  
Vol 215 (1) ◽  
pp. 21-30 ◽  
Author(s):  
J de Jong ◽  
H Stoop ◽  
AJM Gillis ◽  
RJHLM van Gurp ◽  
G-JM van de Geijn ◽  
...  

2005 ◽  
Vol 84 ◽  
pp. S393-S394
Author(s):  
H.W. Choi ◽  
M.R. Shin ◽  
H.S. Lee ◽  
J.W. Cho ◽  
C.K. Lim ◽  
...  

2022 ◽  
Vol 9 ◽  
Author(s):  
Wenhui Ma ◽  
Xin Kang ◽  
Ping Liu ◽  
Kexin She ◽  
Yuanyuan Zhang ◽  
...  

Abstract Caffeine is an important functional substance and is abundant in tea plant, but little is known about how its biosynthesis is regulated by transcription factors. In this study, the NAC-like transcription factor-encoding gene CsNAC7, which is involved in caffeine synthesis, was isolated from a Yinghong 9 cDNA library using a yeast one-hybrid assay; this gene comprises 1371 bp nucleotides and is predicted to encode 456 amino acids. The expression of CsNAC7 at the transcriptional level in tea shoots shared a similar pattern with that of the caffeine synthase gene yhNMT1 in the spring and summer, and its expressed protein was localized in the nucleus. Assays of gene activity showed that CsNAC7 has self-activation activity in yeast, that the active region is at the N-terminus, and that the transient expression of CsNAC7 could significantly promote the expression of yhNMT1 in tobacco leaves. In addition, overexpression or silencing of CsNAC7 significantly increased or decreased the expression of yhNMT1 and the accumulation of caffeine in transgenic tea calli, respectively. Our data suggest that the isolated transcription factor CsNAC7 positively regulates the caffeine synthase gene yhNMT1 and promotes caffeine accumulation in tea plant.


1996 ◽  
Vol 109 (11) ◽  
pp. 2737-2745 ◽  
Author(s):  
V. Chesneau ◽  
A. Prat ◽  
D. Segretain ◽  
V. Hospital ◽  
A. Dupaix ◽  
...  

N-arginine dibasic convertase is a novel metalloendopeptidase which selectively cleaves at the N terminus of arginine residues in paired basic amino acids. Although present in brain and several other tissues, NRD convertase is particularly abundant in testis, where its expression appeared to be restricted to germ cells. Low levels of both mRNA and its corresponding protein were detected early in spermatogenesis. However, a marked accumulation of the protein was observed during late steps (14 to 19) of spermiogenesis. By electron microscopy, the NRD convertase immunoreactivity was localized in the cytoplasm of elongating and elongated spermatids, with a noticeable concentration at the level of two microtubular structures, i.e. the manchette and the axoneme. These observations strongly support the hypothesis that NRD convertase is involved in processing events potentially associated with the morphological transformations occurring during spermiogenesis.


1984 ◽  
Vol 49 (8) ◽  
pp. 1846-1853 ◽  
Author(s):  
Karel Hauzer ◽  
Tomislav Barth ◽  
Linda Servítová ◽  
Karel Jošt

A post-proline endopeptidase (EC 3.4.21.26) was isolated from pig kidneys using a modified method described earlier. The enzyme was further purified by ion exchange chromatography on DEAE-Sephacel. The final product contained about 95% of post-proline endopeptidase. The enzyme molecule consisted of one peptide chain with a relative molecular mass of 65 600 to 70 000, containing a large proportion of acidic and alifatic amino acids (glutamic acid, aspartic acid and leucine) and the N-terminus was formed by aspartic acid or asparagine. In order to prevent losses of enzyme activity, thiol compounds has to be added.


Cell Research ◽  
2021 ◽  
Author(s):  
Xiaoxiao Wang ◽  
Yunlong Xiang ◽  
Yang Yu ◽  
Ran Wang ◽  
Yu Zhang ◽  
...  

AbstractThe pluripotency of mammalian early and late epiblast could be recapitulated by naïve embryonic stem cells (ESCs) and primed epiblast stem cells (EpiSCs), respectively. However, these two states of pluripotency may not be sufficient to reflect the full complexity and developmental potency of the epiblast during mammalian early development. Here we report the establishment of self-renewing formative pluripotent stem cells (fPSCs) which manifest features of epiblast cells poised for gastrulation. fPSCs can be established from different mouse ESCs, pre-/early-gastrula epiblasts and induced PSCs. Similar to pre-/early-gastrula epiblasts, fPSCs show the transcriptomic features of formative pluripotency, which are distinct from naïve ESCs and primed EpiSCs. fPSCs show the unique epigenetic states of E6.5 epiblast, including the super-bivalency of a large set of developmental genes. Just like epiblast cells immediately before gastrulation, fPSCs can efficiently differentiate into three germ layers and primordial germ cells (PGCs) in vitro. Thus, fPSCs highlight the feasibility of using PSCs to explore the development of mammalian epiblast.


Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 338
Author(s):  
Jessica Swanson ◽  
Rennos Fragkoudis ◽  
Philippa C. Hawes ◽  
Joseph Newman ◽  
Alison Burman ◽  
...  

The picornavirus foot-and-mouth disease virus (FMDV) is the causative agent of the economically important disease of livestock, foot-and-mouth disease (FMD). VP4 is a highly conserved capsid protein, which is important during virus entry. Previous published work has shown that antibodies targeting the N-terminus of VP4 of the picornavirus human rhinovirus are broadly neutralising. In addition, previous studies showed that immunisation with the N-terminal 20 amino acids of enterovirus A71 VP4 displayed on the hepatitis B core (HBc) virus-like particles (VLP) can induce cross-genotype neutralisation. To investigate if a similar neutralising response against FMDV VP4 could be generated, HBc VLPs displaying the N-terminus of FMDV VP4 were designed. The N-terminal 15 amino acids of FMDV VP4 was inserted into the major immunodominant region. HBc VLPs were also decorated with peptides of the N-terminus of FMDV VP4 attached using a HBc-spike binding tag. Both types of VLPs were used to immunise mice and the resulting serum was investigated for VP4-specific antibodies. The VLP with VP4 inserted into the spike, induced VP4-specific antibodies, however the VLPs with peptides attached to the spikes did not. The VP4-specific antibodies could recognise native FMDV, but virus neutralisation was not demonstrated. This work shows that the HBc VLP presents a useful tool for the presentation of FMDV capsid epitopes.


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