Article
Computer Science, Artificial Intelligence
Chakkarai Sathyaseelan, L. Ponoop Prasad Patro, Thenmalarchelvi Rathinavelan
Summary: Zinc finger (ZnF) is an important class of nucleic acid and protein recognition domain with diverse structures and biological functions. In order to accurately predict ZnF motifs, researchers collected 74 ZnF sequence patterns and used Pfam HMM profiles for prediction. They developed a web server called ZnF-Prot that can predict 31 ZnF domains in protein sequences of any organism.
PATTERN RECOGNITION
(2023)
Article
Microbiology
Joseph T. Smith Jr, Brianna Tylec, Arunasalam Naguleswaran, Isabel Roditi, Laurie K. Read
Summary: This study reveals the importance of mitochondrial mRNA editing in the developmental regulation of Trypanosoma brucei. The researchers found that temperature reduction and depletion of the differentiation-repressive kinase RDK1 can affect the metabolism of Trypanosoma brucei by altering the editing of mitochondrial cytochrome mRNAs.
Article
Microbiology
Marina Schock, Steffen Schmidt, Klaus Ersfeld
Summary: Trypanosome brucei, the causative agent of African sleeping sickness, has a highly ordered subpellicular microtubule cytoskeleton associated with various proteins regulating morphology, motility, and virulence. Identified protein CAP50 colocalises with microtubules but not with the flagellum, playing a crucial role in maintaining cellular integrity. Depletion of CAP50, along with CAP52 and CAP42, results in defects in cytokinesis, morphology, and microtubule organization.
Review
Biology
Abdurrahman Pharmacy Yusuf, Murtala Bello Abubakar, Ibrahim Malami, Kasimu Ghandi Ibrahim, Bilyaminu Abubakar, Muhammad Bashir Bello, Naeem Qusty, Sara T. Elazab, Mustapha Umar Imam, Athanasios Alexiou, Gaber El-Saber Batiha
Summary: Zinc was established more than half a century ago as an essential micronutrient for normal human physiology, with around 10% of the human proteome potentially binding zinc. Proteins with zinc-binding domains play key roles in epigenetic modifications, such as DNA methylation and histone modifications, regulating transcription under physiological and pathological conditions. Zinc metalloproteins in epigenetics, mainly zinc metalloenzymes and zinc finger proteins, interact as writers, erasers, readers, editors, and feeders to maintain the epigenome's functioning.
Article
Parasitology
Gloria Ceballos-Perez, Miriam Rico-Jimenez, Claudia Gomez-Linan, Antonio M. Estevez
Summary: The zinc finger proteins ZC3H41 and Z41AP play crucial roles in controlling the fate of ribosomal components in response to environmental cues. They interact with multiple proteins and mRNAs, and their binding to target transcripts is weakened under nutritional stress, leading to the accumulation of 5S rRNA precursors and a decrease in protein translation.
PARASITES & VECTORS
(2023)
Article
Multidisciplinary Sciences
Nurit Yaffe, Dvir Rotem, Awakash Soni, Danny Porath, Joseph Shlomai
Summary: This study focused on the condensation of kinetoplast DNA (kDNA), the mitochondrial genome of kinetoplastids, and revealed the role of the replication protein UMSBP in decondensation and initiation of kDNA replication. The condensation of kDNA was found to proceed through a series of hierarchical steps, with multiple local condensation foci assembling into higher order condensation centers, influenced by the maxicircles component of kDNA. The structure of condensing kDNA intermediates shed light on the organization of the condensed kDNA network within the mitochondrial nucleoid.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Nicolas Gonzalez Castro, Jan Bjelic, Gunya Malhotra, Cong Huang, Salman Hasan Alsaffar
Summary: Recent advances in programmable nucleases have driven genome editing from research to clinical and industrial applications. Each technology has its distinct characteristics and safety is a paramount consideration, with comprehensive off-target detection strategies being crucial for ensuring safety in all applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Shiheng Liu, Hong Wang, Xiaorun Li, Fan Zhang, Jane K. J. Lee, Zihang Li, Clinton Yu, Jason J. Hu, Xiaojing Zhao, Takuma Suematsu, Ana L. Alvarez-Cabrera, Qiushi Liu, Liye Zhang, Lan Huang, Inna Aphasizheva, Ruslan Aphasizhev, Z. Hong Zhou
Summary: The mechanism of information transfer from gRNA to mRNA in Trypanosoma brucei has been revealed using cryo-electron microscopy and functional studies, providing insights into the binding and processing of gRNA-mRNA complexes.
Article
Biotechnology & Applied Microbiology
Jiyeon Kweon, Hye-Yeon Hwang, Haesun Ryu, An-Hee Jang, Daesik Kim, Yongsub Kim
Summary: Researchers developed a method using prime editor 2 nuclease (PE2 nuclease) and paired pegRNA to achieve programmable chromosomal translocations and inversions. They successfully introduced DNA recombination and precise chromosomal translocations in human cells. This method can be used to create cancer-associated translocations and inversions as well as for disease modeling or gene therapy.
Article
Plant Sciences
Andrew B. Gipson, Maureen R. Hanson, Stephane Bentolila
Summary: OZ1 is a crucial protein involved in multiple RNA editing events in the chloroplast, interacting primarily with PPR proteins through its Znf domains and unique C-terminal region. Truncation assays of OZ1 revealed the necessity of its Znf domains for restoring chloroplast RNA editing in vivo, highlighting their key role in the editing process and interaction with RNA-binding factors like ORRM1. These findings contribute to a better understanding of the chloroplast plant editosome model.
Review
Pharmacology & Pharmacy
Flavia Nathiely Silveira Fachel, Lariane Francio, Edina Poletto, Roselena Silvestri Schuh, Helder Ferreira Teixeira, Roberto Giugliani, Guilherme Baldo, Ursula Matte
Summary: This article reviews the clinical and molecular characteristics of lysosomal storage disorders, with a focus on mucopolysaccharidoses, and discusses the use of gene editing techniques to ameliorate their symptoms. Early results of clinical trials suggest that gene therapy may have a significant impact on the future treatment of these diseases, although hurdles related to specific hard-to-reach organs still need to be overcome.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Article
Chemistry, Medicinal
Miriam Yague-Capilla, Victor M. Castillo-Acosta, Cristina Bosch-Navarrete, Luis Miguel Ruiz-Perez, Dolores Gonzalez-Pacanowska
Summary: The study characterized the unique trypanosomal SAMHD1 orthologue TbHD52 as essential in maintaining pyrimidine dNTP homeostasis and contributing to cellular dTTP biosynthesis. Knockout of TbHD52 results in cellular dysfunction, which can be rescued by overexpression of human dCMP deaminase.
ACS INFECTIOUS DISEASES
(2021)
Article
Multidisciplinary Sciences
Amit Kumar Gaurav, Marjia Afrin, Xian Yang, Arpita Saha, S. K. Abdus Sayeed, Xuehua Pan, Zeyang Ji, Kam-Bo Wong, Mingjie Zhang, Yanxiang Zhao, Bibo Li
Summary: Trypanosoma brucei is a protozoan parasite that causes human African trypanosomiasis. TbRAP1, a telomere protein, has been shown to silence VSG genes by binding to dsDNA. However, the mechanism by which TbRAP1 allows the expression of a single active VSG gene was unknown. In this study, the researchers unexpectedly discovered an RNA Recognition Motif (RRM) in TbRAP1, which is unprecedented for RAP1 homologs. They found that TbRAP1 RRM, assisted by a specific patch, can recognize and bind to the 3'UTR sequences of VSG genes. Mutating the conserved residues in RRM abolished RNA binding activity, significantly decreased the level of active VSG RNA, and derepressed silent VSG genes. Their findings suggest a monoallelic expression mechanism for VSG genes, in which the abundant RNA of the active VSG gene antagonizes TbRAP1's silencing effect.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Katherine Sortino, Brianna L. Tylec, Runpu Chen, Yijun Sun, Laurie K. Read
Summary: Uridine insertion/deletion RNA editing is a common post-transcriptional modification in kinetoplastid organisms. The RESC complex plays an important role in this process by modulating protein and RNA interactions. In this study, the roles of RESC13 and RESC14 are further explored using high-throughput sequencing on multiple transcripts. The findings suggest that RESC13 and RESC14 have both conserved and transcript-specific effects in editing.
Article
Microbiology
Nuria W. Negrao, Logan P. Crowe, Brian S. Mantilla, Rodrigo P. Baptista, Sharon King-Keller, Guozhong Huang, Roberto Docampo
Summary: Trypanosoma brucei is the causative agent of African trypanosomiasis, and there is a need for new drugs due to limited treatment options and evidence of resistance. A phosphoinositide phospholipase C (TbPI-PLC-like) with an X and PDZ domain was discovered, similar to TbPI-PLC1. Recombinant TbPI-PLC-like does not hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP2) and does not modulate TbPI-PLC1 activity, but its knockdown affects the proliferation of trypanosomes.