A processed short transcript of Leishmania, ODD1

Iribar, M.P.; Tosi, Luiz Ricardo Orsini; Cruz, Ângela K.

doi:10.1016/s0166-6851(03)00006-9

Cited by 8 publications

(5 citation statements)

References 14 publications

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“…Selenoproteins are a group of enzymes bearing selenocysteine in their catalytic domain. Many of the Se-bearing proteins participate in oxidative stress protection as observed in Leishmania parasites (Iribar et al ., 2003 ; Da Silva et al ., 2014 ). The use of leishmanial selenoproteins and selenoamino acid (selenomethionine) as therapeutic targets due to their role in modulation and evasion of the host immune responses has been recently suggested (Rashidi et al ., 2020 a , 2020 b ).…”

Section: From Potential Targets To Drug Repurposingmentioning

confidence: 99%

Potential therapeutic targets shared between leishmaniasis and cancer

et al. 2021

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Section: From Potential Targets To Drug Repurposingmentioning

confidence: 99%

Potential therapeutic targets shared between leishmaniasis and cancer

et al. 2021

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“…The first suggestion that Kinetoplastidae have Sec synthesis machinery originated from the identification of an RNA transcript in, named ODD1, of unknown function in Leishmania major cells which contains in-frame UGA stop codons and a putative SECIS element [4]. The identification of homologous genes encoding proteins involved in Sec synthesis, such as SELD, SELB, and PSTK, in Leishmania and Trypanosoma genomes, as well as the two putative selenoprotein genes (LmSel1, LinfSel1 of L. major and L. infantum respectively) strongly support the existence of a complete selenocysteine synthesis pathway in these organisms [11].…”

Section: Selenocysteine Biosynthesis and Its Spe-cific Incorporation mentioning

confidence: 99%

“…The selenocysteine synthesis pathway was first described in Leishmania in 2006 [4], and the existence of three selenoproteins in Kinetoplastida, two with mammalian homologs, SelK and SelT, and a third, SelTryp, exclusive to Kinetoplastida were proposed later [5]. Auranofin, a selective inhibitor of selenoproteins, strongly inhibits the growth of Trypanosoma brucei cultures [5], indicating the existence of a similar pathway in that species.…”

Section: Introductionmentioning

confidence: 99%

Biological Implications of Selenium and its Role in Trypanosomiasis Treatment

Silva¹,

Silva²,

Thiemann³

2014

CMC

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Selenium (Se) is an essential trace element for several organisms and is present in proteins as selenocysteine (Sec or U), an amino acid that is chemically distinct from serine and cysteine by a single atom (Se instead of O or S, respectively). Sec is incorporated into selenoproteins at an in-frame UGA codon specified by an mRNA stem-loop structure called the selenocysteine incorporating sequence (SECIS) presented in selenoprotein mRNA and specific selenocysteine synthesis and incorporation machinery. Selenoproteins are presented in all domains but are not found in all organisms. Although several functions have been attributed to this class, the majority of the proteins are involved in oxidative stress defense. Here, we discuss the kinetoplastid selenocysteine pathway and how selenium supplementation is able to alter the infection course of trypanosomatids in detail. These organisms possess the canonical elements required for selenoprotein production such as phosphoseryl tRNA kinase (PSTK), selenocysteine synthase (SepSecS), selenophosphase synthase (SelD or SPS), and elongation factor EFSec (SelB), whereas other important factors presented in mammal cells, such as SECIS binding protein 2 (SBP) and SecP 43, are absent. The selenoproteome of trypanosomatids is small, as is the selenoproteome of others parasites, which is in contrast to the large number of selenoproteins found in bacteria, aquatic organisms and higher eukaryotes. Trypanosoma and Leishmania are sensitive to auranofin, a potent selenoprotein inhibitor; however, the probable drug mechanism is not related to selenoproteins in kinetoplastids. Selenium supplementation decreases the parasitemia of various Trypanosome infections and reduces important parameters associated with diseases such as anemia and parasite-induced organ damage. New experiments are necessary to determine how selenium acts, but evidence suggests that immune response modulation and increased host defense against oxidative stress contribute to control of the parasite infection.

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“…Although it has been 30 years since the first functional eukaryotic ncRNA was discovered (BRANNAN et al, 1990), only a few ncRNAs have been detected in trypanosomatids (IRIBAR; TOSI; CRUZ, 2003;DUMAS et al, 2006;ZHENG et al, 2013;FREITAS CASTRO et al, 2017;CHIKNE et al, 2019;GUEGAN et al, 2022). A small nucleolar ncRNA regulates differentiation in Trypanosoma brucei parasites by manipulating the expression of two essential differentiation factors (GUEGAN et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

A short noncoding RNA modulates gene expression and affects stress response and parasite differentiation inLeishmania braziliensis

Quilles,

Espada,

Orsine

et al. 2024

Preprint

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The protozoan parasiteLeishmaniaspp. is a causative agent of leishmaniasis, a disease that affects millions of people in more than 80 countries worldwide. Apart from its medical relevance, this organism has a genetic organization that is unique among eukaryotes. Studies of the mechanisms regulating gene expression in Leishmania led us to investigate noncoding RNAs (ncRNAs) as regulatory elements. We previously identified differentially expressed (DE) ncRNAs inLeishmania braziliensiswith potential roles in the parasite biology and development. Herein, we present a functional analysis of one such DE ncRNA, the 147-nucleotide-long transcript ncRNA97, which is preferentially expressed in amastigotes, the replicative form within mammalian phagocytes. By RT-qPCR the ncRNA97 was detected in greater quantities in the nucleus under physiological conditions and in the cytoplasm under nutritional stress. Interestingly, the transcript is protected at the 5' end but is not processed by the canonical trypanosomatid trans-splicing mechanism, according to the RNA circularization assay. ncRNA97 knockout (KO) and addback (AB) transfectants were generated and subjected to phenotypic analysis, which revealed that ncRNA97 impairs the starvation response and differentiation to the infective form. Comparative transcriptomics of ncRNA97KO and parental cells revealed that transcripts encoding amastigote-specific proteins were affected. This pioneering work demonstrates that ncRNAs contribute to the developmental regulatory mechanisms ofLeishmania.

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A processed short transcript of Leishmania, ODD1

Cited by 8 publications

References 14 publications

Potential therapeutic targets shared between leishmaniasis and cancer

Potential therapeutic targets shared between leishmaniasis and cancer

Biological Implications of Selenium and its Role in Trypanosomiasis Treatment

A short noncoding RNA modulates gene expression and affects stress response and parasite differentiation inLeishmania braziliensis

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