The RNA-binding protein RBP42 regulates cellular energy metabolism in mammalian-infective Trypanosoma brucei
RNA-binding proteins (RBPs) are key players in coordinated post-transcriptional regulation of functionally related genes, defined as RNA regulons. RNA regulons play particularly critical roles in parasitic trypanosomes, which exhibit unregulated co-transcription of long unrelated gene arrays. In thi...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-10-01
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| Series: | mSphere |
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| Online Access: | https://journals.asm.org/doi/10.1128/msphere.00273-23 |
| _version_ | 1797651070350000128 |
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| author | Anish Das Tong Liu Hong Li Seema Husain |
| author_facet | Anish Das Tong Liu Hong Li Seema Husain |
| author_sort | Anish Das |
| collection | DOAJ |
| description | RNA-binding proteins (RBPs) are key players in coordinated post-transcriptional regulation of functionally related genes, defined as RNA regulons. RNA regulons play particularly critical roles in parasitic trypanosomes, which exhibit unregulated co-transcription of long unrelated gene arrays. In this report, we present a systematic analysis of an essential RBP, RBP42, in the mammalian-infective bloodstream form of African trypanosome and show that RBP42 is a key regulator of parasite’s central carbon and energy metabolism. Using individual-nucleotide resolution UV cross-linking and immunoprecipitation to identify genome-wide RBP42-RNA interactions, we show that RBP42 preferentially binds within the coding region of mRNAs encoding core metabolic enzymes. Global quantitative transcriptomic and proteomic analyses reveal that loss of RBP42 reduces the abundance of target mRNA-encoded proteins, but not target mRNA, suggesting a positive translational regulatory role of RBP42. Significant changes in central carbon metabolic intermediates, following loss of RBP42, further support its critical role in cellular energy metabolism. Trypanosoma brucei infection, transmitted through the bite of blood-feeding tsetse flies, causes deadly diseases in humans and livestock. This disease, if left untreated, is almost always fatal. Existing therapies are toxic and difficult to administer. During T. brucei’s lifecycle in two different host environments, the parasite progresses through distinctive life stages with major morphological and metabolic changes, requiring precise alteration of parasite gene expression program. In the absence of regulated transcription, post-transcriptional processes mediated by RNA-binding proteins play critical roles in T. brucei gene regulation. In this study, we show that the RNA-binding protein RBP42 plays crucial roles in cellular energy metabolic regulation of this important human pathogen. Metabolic dysregulation observed in RBP42 knockdown cells offers a breadth of potential interest to researchers studying parasite biology and can also impact research in general eukaryotic biology. |
| first_indexed | 2024-03-11T16:09:44Z |
| format | Article |
| id | doaj.art-e4bdc741f49545a797d4e93d9512075f |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-03-11T16:09:44Z |
| publishDate | 2023-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-e4bdc741f49545a797d4e93d9512075f2023-10-24T16:32:15ZengAmerican Society for MicrobiologymSphere2379-50422023-10-018510.1128/msphere.00273-23The RNA-binding protein RBP42 regulates cellular energy metabolism in mammalian-infective Trypanosoma bruceiAnish Das0Tong Liu1Hong Li2Seema Husain3Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers-New Jersey Medical School , Newark, New Jersey, USACenter for Advanced Proteomics Research, Rutgers-New Jersey Medical School , Newark, New Jersey, USACenter for Advanced Proteomics Research, Rutgers-New Jersey Medical School , Newark, New Jersey, USAGenomics Center, Rutgers-New Jersey Medical School , Newark, New Jersey, USARNA-binding proteins (RBPs) are key players in coordinated post-transcriptional regulation of functionally related genes, defined as RNA regulons. RNA regulons play particularly critical roles in parasitic trypanosomes, which exhibit unregulated co-transcription of long unrelated gene arrays. In this report, we present a systematic analysis of an essential RBP, RBP42, in the mammalian-infective bloodstream form of African trypanosome and show that RBP42 is a key regulator of parasite’s central carbon and energy metabolism. Using individual-nucleotide resolution UV cross-linking and immunoprecipitation to identify genome-wide RBP42-RNA interactions, we show that RBP42 preferentially binds within the coding region of mRNAs encoding core metabolic enzymes. Global quantitative transcriptomic and proteomic analyses reveal that loss of RBP42 reduces the abundance of target mRNA-encoded proteins, but not target mRNA, suggesting a positive translational regulatory role of RBP42. Significant changes in central carbon metabolic intermediates, following loss of RBP42, further support its critical role in cellular energy metabolism. Trypanosoma brucei infection, transmitted through the bite of blood-feeding tsetse flies, causes deadly diseases in humans and livestock. This disease, if left untreated, is almost always fatal. Existing therapies are toxic and difficult to administer. During T. brucei’s lifecycle in two different host environments, the parasite progresses through distinctive life stages with major morphological and metabolic changes, requiring precise alteration of parasite gene expression program. In the absence of regulated transcription, post-transcriptional processes mediated by RNA-binding proteins play critical roles in T. brucei gene regulation. In this study, we show that the RNA-binding protein RBP42 plays crucial roles in cellular energy metabolic regulation of this important human pathogen. Metabolic dysregulation observed in RBP42 knockdown cells offers a breadth of potential interest to researchers studying parasite biology and can also impact research in general eukaryotic biology.https://journals.asm.org/doi/10.1128/msphere.00273-23RNA-binding proteinRBP42iCLIPRNA regulonTrypanosomaprotozoa |
| spellingShingle | Anish Das Tong Liu Hong Li Seema Husain The RNA-binding protein RBP42 regulates cellular energy metabolism in mammalian-infective Trypanosoma brucei mSphere RNA-binding protein RBP42 iCLIP RNA regulon Trypanosoma protozoa |
| title | The RNA-binding protein RBP42 regulates cellular energy metabolism in mammalian-infective Trypanosoma brucei |
| title_full | The RNA-binding protein RBP42 regulates cellular energy metabolism in mammalian-infective Trypanosoma brucei |
| title_fullStr | The RNA-binding protein RBP42 regulates cellular energy metabolism in mammalian-infective Trypanosoma brucei |
| title_full_unstemmed | The RNA-binding protein RBP42 regulates cellular energy metabolism in mammalian-infective Trypanosoma brucei |
| title_short | The RNA-binding protein RBP42 regulates cellular energy metabolism in mammalian-infective Trypanosoma brucei |
| title_sort | rna binding protein rbp42 regulates cellular energy metabolism in mammalian infective trypanosoma brucei |
| topic | RNA-binding protein RBP42 iCLIP RNA regulon Trypanosoma protozoa |
| url | https://journals.asm.org/doi/10.1128/msphere.00273-23 |
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