The mRNA-bound Proteome of Leishmania mexicana: Novel Genetic Insight into an Ancient Parasite
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Pablos Torró, Luis Miguel de; Ferreira, Tiago R.; Dowle, Adam A.; Forrester, Sarah; Parry, Ewan; Newling, Katherine; Walrad, Pegine B.Editorial
The American Society for Biochemistry and Molecular Biology, Inc.
Fecha
2019-07Referencia bibliográfica
De Pablos, L. M., Ferreira, T. R., Dowle, A. A., Forrester, S., Parry, E., Newling, K., & Walrad, P. B. (2019). The mRNA-bound proteome of Leishmania mexicana: novel genetic insight into an ancient parasite. Molecular & Cellular Proteomics, 18(7), 1271-1284.
Patrocinador
This work was supported by the Medical Research Council [grant number MR/L00092X/1 to PBW]. Funding for open access charge: Medical Research Council and University of York. LCMS within the York Centre of Excellence in Mass Spectrometry was founded through Science City York and Yorkshire Forward/Northern Way Initiative; and is supported by EPSRC [grant numbers EP/K039660/1, EP/M028127/1].Resumen
Leishmania parasite infections, termed the leishmaniases,
cause significant global infectious disease burden.
The lifecycle of the parasite embodies three main
stages that require precise coordination of gene regulation
to survive environmental shifts between sandfly
and mammalian hosts. Constitutive transcription in kinetoplastid
parasites means that gene regulation is overwhelmingly
reliant on post-transcriptional mechanisms,
yet strikingly few Leishmania trans-regulators are
known. Using optimized crosslinking and deep, quantified
mass spectrometry, we present a comprehensive
analysis of 1400 mRNA binding proteins (mRBPs) and
whole cell proteomes from the three main Leishmania
lifecycle stages. Supporting the validity, although the
crosslinked RBPome is magnitudes more enriched, the
protein identities of the crosslinked and non-crosslinked
RBPomes were nearly identical. Moreover, multiple
candidate RBPs were endogenously tagged and
found to associate with discrete mRNA target pools in a
stage-specific manner. Results indicate that in L. mexicana
parasites, mRNA levels are not a strong predictor
of the whole cell expression or RNA binding potential of
encoded proteins. Evidence includes a low correlation
between transcript and corresponding protein expression
and stage-specific variation in protein expression
versus RNA binding potential. Unsurprisingly, RNA binding
protein enrichment correlates strongly with relative
replication efficiency of the specific lifecycle stage. Our
study is the first to quantitatively define and compare
the mRBPome of multiple stages in kinetoplastid parasites.
It provides novel, in-depth insight into the transregulatory
mRNA:Protein (mRNP) complexes that drive
Leishmania parasite lifecycle progression