RNA in development: how ribonucleoprotein granules regulate the life cycles of pathogenic protozoa

Abstract

Ribonucleoprotein (RNP) granules are important posttranscriptional regulators of messenger RNA (mRNA) fate. Several types of RNP granules specifically regulate gene expression during development of multicellular organisms and are commonly referred to as germ granules. The function of germ granules is not entirely understood and probably diverse, but it is generally agreed that one main function is posttranscriptional regulation of gene expression during early development, when transcription is silent. One example is the translational repression of maternally derived mRNAs in oocytes. Here, I hope to show that the need for regulation of gene expression by RNP granules is not restricted to animal development, but plays an equally important role during the development of pathogenic protozoa. Apicomplexa and Trypanosomatidae have complex life cycles with frequent host changes. The need to quickly adapt gene expression to a new environment as well as the ability to suppress translation to survive latencies is critical for successful completion of life cycles. Posttranscriptional gene regulation is not necessarily simpler in protozoa. Apicomplexa surprise with the presence of micro RNA (miRNAs) and upstream open reading frames (µORFs). Trypanosomes have an unusually large repertoire of different RNP granule types. A better understanding of RNP granules in protozoa may help to gain insight into the evolutionary origin of RNP granules: Trypanosomes for example have two types of granules with interesting similarities to animal germ granules.

Translational Control in the Latency of Apicomplexan Parasites

“…It is notable that eIF2 phosphorylation and mRNP granules accompany differentiation in the kinetoplastids such as Trypanosoma cruzi and Leishmania infantum , and eIF2 phosphorylation has also been implicated in Entamoeba spp. encystation [89,107–111]. Key priorities for the future include the identification of downstream ISR effectors in these parasites as well as determining which kinases and naturally occurring environmental signals mediate each specific developmental transition (see Outstanding Questions).…”

“…Distinct from stress granules, germ granules are mRNP cytoplasmic foci that contain stably repressed transcripts for extended periods of time and are commonly seen in metazoan oocytes before their fertilization [89,90]. Like persistent latent parasite stages, animal oocytes also exist in a non-replicative state for an extended period of time and maintain a steady pool of repressed transcripts that are necessary for developmental progression [89].…”

“…Like persistent latent parasite stages, animal oocytes also exist in a non-replicative state for an extended period of time and maintain a steady pool of repressed transcripts that are necessary for developmental progression [89]. Many parallels can be drawn between classic germ granules and the germ-like granules that have been shown in Plasmodium because they are similar in both composition and function.…”

Transcript maturation in apicomplexan parasites

“…There are extensive RNA-based machineries in these parasites responsible for transcript maturation (splicing, mRNA capping and polyadenylation) and mRNA stabilization (protection, degradation) that may act in accord with translational control (RNP granules, μORFs, and mi-RNAs) in order to coordinate cell cycle gene expression profiles. There are excellent reviews of Apicomplexa translation control [11], therefore, here we will focus on nuclear mRNA processing with emphasis on the splicing machineries and their regulation.…”

Cytoplasmic RNA Granules in Somatic Maintenance

“…The life cycles of Apicomplexa (several Plasmodium strains cause malaria in humans, Toxoplasma gondii – toxoplasmosis) and Trypanosomatidae ( Trypanosoma brucei – sleeping sickness; T. cruzi – Chagas disease; Leishmania – leishmaniasis) necessitates the switch of host organisms [58]. This requires the rapid adjustment to new environments and is accompanied by stress for the parasite.…”