A new twist in trypanosome RNA metabolism: cis-splicing of pre-mRNA

Mair, Gunnar R.; Shi, Huafang; Li, Hongjie; Djikeng, Appolinaire; Avilés, Hernán; Bishop, Joseph R.; Falcone, Franco H.; Gavrilescu, Cristina Maria; Montgomery, Jacqui; Santori, Maria Isabel; Stern, Leah S.; Wang, Zefeng; Ullu, Elisabetta; Tschudi, Christian

doi:10.1017/s135583820099229x

Cited by 147 publications

(130 citation statements)

References 23 publications

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“…In trypanosomes, all the RNAs are processed by a mechanism different from that in mammals (cis-splicing) called trans-splicing, a process that involves the union of the exons in two independent transcripts. However, in recent studies it was observed that cis-splicing can also occur in the gene PAP (poly-A polymerase) of Trypanosoma brucei and T. cruzi, suggesting that both trans and cis-splicing, occur in these parasites, with a predominance of trans-splicing (Mair et al 2000).The SL RNA or miniexon is a primary transcript synthesized independently of pre-mRNA and trans-spliced in all nuclear mRNA. The majority of mRNAs is synthesized as polycistronic precursors (Agabian 1990).…”

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confidence: 99%

Trypanosoma cruzi: establishment of permeable cells for RNA processing analysis with drugs

Ambrósio

Barbosa

Vianna

et al. 2004

Mem. Inst. Oswaldo Cruz

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Pre-mRNA maturation in trypanosomatids occurs through a process called trans-splicing which involves excision of introns and union of exons in two independentIn the process of pre-mRNA maturation, known as splicing, the introns (non-coding regions of polypeptides) are removed from primary transcripts and the exons (coding regions) joined to form a contiguous sequence specifying a functional polypeptide. It was observed that the process is dependent on ribonucleoproteins, small molecules of RNA binding proteins with different forms and sizes, assembling a macromolecular complex called the spliceosome, where the maturation reaction takes place (Leningher et al. 1995). In trypanosomes, all the RNAs are processed by a mechanism different from that in mammals (cis-splicing) called trans-splicing, a process that involves the union of the exons in two independent transcripts. However, in recent studies it was observed that cis-splicing can also occur in the gene PAP (poly-A polymerase) of Trypanosoma brucei and T. cruzi, suggesting that both trans and cis-splicing, occur in these parasites, with a predominance of trans-splicing (Mair et al. 2000).The SL RNA or miniexon is a primary transcript synthesized independently of pre-mRNA and trans-spliced in all nuclear mRNA. The majority of mRNAs is synthesized as polycistronic precursors (Agabian 1990). T. brucei SL RNA contains an unusual cap structure consisting of 7-methylguanosine linked to four modified nucleosides. This modification of trypanosomatid SL sequence might be required for the function of the SL RNA in trans-splic-

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confidence: 99%

Trypanosoma cruzi: establishment of permeable cells for RNA processing analysis with drugs

Ambrósio

Barbosa

Vianna

et al. 2004

Mem. Inst. Oswaldo Cruz

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“…Since no removal of introns is necessary in the mRNA processing of T. cruzi, alternative cis-splicing should be uncommon. Until now, few experimental works have demonstrated alterations in protein composition due to alternative cis-splicing (Mair et al 2000). 2: Additional trans-splicing in T. cruzi occur more frequently in rp genes.…”

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confidence: 99%

Trypanosomatid EST: a neglected information resource regarding flagellated protozoa?

Brandão

2008

Mem. Inst. Oswaldo Cruz

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“…To investigate whether cis-splicing was also affected upon silencing the two proteins, we performed RT-PCR to detect the effects on the level of the PAP transcript, which undergoes both cis-and trans-splicing (26). The results, presented in Fig.…”

Section: Fig 4 the Level Of Sl Rna And The Y-structure Intermediatementioning

confidence: 99%

“…Trans-splicing evolved to separate long polycistronic transcripts. In trypanosomes, all mRNAs undergo trans-splicing, but cis-splicing also exists (26). All spliceosomal U snRNAs were identified in this organism (24).…”

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confidence: 94%

Identification and Functional Characterization of Lsm Proteins in Trypanosoma brucei

Liu¹,

Liang²,

Uliel

et al. 2004

Journal of Biological Chemistry

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RNA interference of Sm proteins inTrypanosoma brucei demonstrated that the stability of the small nuclear RNAs (U1, U2, U4, U5) and the spliced leader RNA, but not U6 RNA, were affected upon Sm depletion (Mandelboim, M., Barth, S., Biton, M., Liang, X. H., and Michaeli, S. (2003) J. Biol. Chem. 278, 51469-51478), suggesting that Lsm proteins that bind and stabilize U6 RNA in other eukaryotes should exist in trypanosomes. In this study, we identified seven Lsm proteins (Lsm2p to Lsm8p) and examined the function of Lsm3p and Lsm8p by RNA interference silencing. Both Lsm proteins were found to be essential for U6 stability and mRNA decay. Silencing was lethal, and cisand trans-splicing were inhibited. Importantly, silencing also affected the level of U4.U6 and the U4.U6/U5 tri-small nuclear ribonucleoprotein complexes. The presence of Lsm proteins in trypanosomes that diverged early in the eukaryotic lineage suggests that these proteins are highly conserved in both structure and function among eukaryotes. Interestingly, however, Lsm1p that is specific to the mRNA decay complex was not identified in the genome data base of any kinetoplastidae, and the Lsm8p that in other eukaryotes exclusively functions in U6 stability was found to function in trypanosomes also in mRNA decay. These data therefore suggest that in trypanosomes only a single Lsm complex may exist.

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A new twist in trypanosome RNA metabolism: cis-splicing of pre-mRNA

Abstract: It has been known for almost a decade and a half that in trypanosomes all

Cited by 147 publications

References 23 publications

Trypanosoma cruzi: establishment of permeable cells for RNA processing analysis with drugs

Trypanosoma cruzi: establishment of permeable cells for RNA processing analysis with drugs

Trypanosomatid EST: a neglected information resource regarding flagellated protozoa?

Identification and Functional Characterization of Lsm Proteins in Trypanosoma brucei

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