The wide expansion of hepatitis delta virus-like ribozymes throughout trypanosomatid genomes is linked to the spreading of L1Tc/ingi clade mobile elements.

Francisco José Sánchez-Luque,Patricia Eugenia Carreira,Manuel Carlos López,Carlos Alonso,María Carmen Thomas

doi:10.1186/1471-2164-15-340

Abstract

BackgroundHepatitis Delta Virus (HDV)-like ribozymes have recently been found in many mobile elements in which they take part in a mechanism that releases intermediate RNAs from cellular co-transcripts. L1Tc in Trypanosoma cruzi is one of the elements in which such a ribozyme is located. It lies in the so-called Pr77-hallmark, a conserved region shared by retrotransposons belonging to the trypanosomatid L1Tc/ingi clade. The wide distribution of the Pr77-hallmark detected in trypanosomatid retrotransposons renders the potential catalytic activity of these elements worthy of study: their distribution might contribute to host genetic regulation at the mRNA level. Indeed, in Leishmania spp, the pervasive presence of these HDV-like ribozyme-containing mobile elements in certain 3′-untranslated regions of protein-coding genes has been linked to mRNA downregulation.ResultsIntensive screening of publicly available trypanosomatid genomes, combined with manual folding analyses, allowed the isolation of putatively Pr77-hallmarks with HDV-like ribozyme activity. This work describes the conservation of an HDV-like ribozyme structure in the Pr77 sequence of retrotransposons in a wide range of trypanosomatids, the catalytic function of which is maintained in the majority.These results are consistent with the previously suggested common phylogenetic origin of the elements that belong to this clade, although in some cases loss of functionality appears to have occurred and/or perhaps molecular domestication by the host.ConclusionsThese HDV-like ribozymes are widely distributed within retrotransposons across trypanosomatid genomes. This type of ribozyme was once thought to be rare in nature, but in fact it would seem to be abundant in trypanosomatid transcripts. It can even form part of the pool of mRNA 3′-untranslated regions, particularly in Leishmania spp. Its putative regulatory role in host genetic expression is discussed.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-340) contains supplementary material, which is available to authorized users.

Highlights

Hepatitis Delta Virus (HDV)-like ribozymes have recently been found in many mobile elements in which they take part in a mechanism that releases intermediate RNAs from cellular co-transcripts
This paper reports that HDV-like ribozymes are present in most of the L1Tc/ingi clade retrotransposons, which are ubiquitous in trypanosomatids
Identification of putatively active HDV-like ribozyme candidates related to the L1Tc/ingi clade in trypanosomatids A bioinformatic BLAST search of the Eukaryotic Pathogen Resources Database (EuPathDB) was used to search for Pr77 homologues in mobile elements of different trypanosomatid genomes (T. brucei, T. congolense, T. vivax, Leishmania major, Leishmania donovani, Leishmania infantum, Leishmania tarentolae, Leishmania braziliensis, Leishmania panamensis and Leishmania mexicana)

Summary

Introduction

Hepatitis Delta Virus (HDV)-like ribozymes have recently been found in many mobile elements in which they take part in a mechanism that releases intermediate RNAs from cellular co-transcripts. Non-long terminal repeat (non-LTR) retrotransposons mobilise using a target-primed reverse transcription (TPRT) mechanism involving the use of the 3′ hydroxyl group at a DNA break to prime the reverse transcription of their RNAs [1]. LINEs are mobilised in an autonomous fashion by the retrotransposition machinery they encode They contain one or two open reading frames (ORF) and are transcribed and translated by the cellular machinery. SINEs are either products of LINE ORF deletion, with preservation of the LINE sequence 5′- and 3′-ends ( referred to as short, internally deleted elements or SIDEs [3]; Figure 1A) or chimeras of cellular, viral or other transposable element RNAs (e.g., Alu, SVA, 5SrRNA- and tRNA-chimeric elements) that carry an internal promoter in the 5′-end region [4,5,6]

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