Biology subjects

Redrejo-Rodriguez, M.

Publications and source records attributed to Redrejo-Rodriguez, M..

3 recordsLinked to original sources

bioRxiv2022

Multiple Ciliary Localization Signals Control INPP5E Ciliary Targeting

Primary cilia are sensory membrane protrusions whose dysfunction causes diseases named ciliopathies. INPP5E is a ciliary phosphoinositide phosphatase mutated in ciliopathies like Joubert syndrome. INPP5E regulates numerous ciliary functions, such as cilium stability, trafficking, signaling, or exovesicle release. Despite its key ciliary roles, how INPP5E accumulates in cilia remains poorly understood. Herein, we show that INPP5E ciliary targeting requires its folded catalytic domain and is controlled by four ciliary localization signals (CLSs), the first two of which we newly discover: LLxPIR motif (CLS1), W383 (CLS2), FDRxLYL motif (CLS3) and CaaX box (CLS4). We answer two long-standing questions in the field. First, partial redundancy between CLS1 and CLS4 explains why CLS4 is dispensable for ciliary targeting. Second, the essential need for CLS2 on the catalytic domain surface clarifies why CLS3 and CLS4 are together insufficient for ciliary accumulation. Furthermore, we reveal that some Joubert syndrome mutations in INPP5E catalytic domain affect its ciliary targeting, and shed light on the mechanisms of action of each CLS. Thus, we find that CLS2 and CLS3 promote interaction with TULP3 and ARL13B, while downregulating CEP164 binding. On the other hand, CLS4 recruits PDE6D, RPGR and ARL13B, and cooperates with CLS1 in ATG16L1 binding. Lastly, we show INPP5E immune synapse targeting is CLS-independent. Altogether, we reveal unusual complexity in INPP5E ciliary targeting mechanisms, likely reflecting its multiple key roles in ciliary biology.

cell biology↗

bioRxiv2021

UG/Abi: a highly diverse family of prokaryotic reverse transcriptases associated with defense functions

Reverse transcriptases (RTs) are enzymes capable of synthesizing DNA using RNA as a template. Within the last few years, a burst of research has led to the discovery of novel prokaryotic RTs with diverse antiviral properties, such as DRTs (Defense-associated RTs), which belong to the so-called group of unknown RTs (UG) and are closely related to the Abortive Infection system (Abi) RTs. In this work, we performed a systematic analysis of UG and Abi RTs, increasing the number of UG/Abi members up to 42 highly diverse groups, most of which are predicted to be functionally associated with other gene(s) or domain(s). Based on this information, we classified these systems into three major classes. In addition, we reveal that most of these groups are associated with defense functions and/or mobile genetic elements, and demonstrate the antiphage role of four novel groups. Besides, we highlight the presence of one of these systems in novel families of human gut viruses infecting members of the Bacteroidetes and Firmicutes phyla. This work lays the foundation for a comprehensive and unified understanding of these highly diverse RTs with enormous biotechnological potential.

evolutionary biology↗

bioRxiv2020

The fully resolved genome of Bacillus thuringiensis HER1410 reveals a cry-containing chromosome, two megaplasmids & an integrative plasmidial prophage

Bacillus thuringiensis is the most used biopesticide in agriculture. Its entomopathogenic capacity stems from the possession of plasmid-borne insecticidal crystal genes (cry), traditionally used as discriminant taxonomic feature for that species. As such, crystal and plasmid identification are key to the characterization of this species. To date, about 600 B. thuringiensis genomes have been reported, but less than 5% have been resolved, while the other draft genomes are incomplete, precluding plasmid delineation. Here we present the complete genome of Bacillus thuringiensis HER1410, a strain closely related to B. thuringiensis entomocidus and a known host for a variety of Bacillus phages. The combination of short and long-reads techniques allowed fully resolving the genome and delineation of three plasmids. This enabled the accurate detection of an unusual location of a unique cry gene, cry1Ba4, located in a genomic island near the chromosome replication origin. Two megaplasmids, pLUSID1 and pLUSID2 could be delineated: pLUSID1 (368kb), a likely conjugative plasmid involved in virulence, and pLUSID2 potentially related to the sporulation process. A smaller plasmidial prophage pLUSID3, with a dual lifestyle whose integration within the chromosome, causes the disruption of a flagellar key component. Finally, phylogenetic analysis located this strain within a clade comprising members from the B. thuringiensis serovar thuringiensis and other serovars and with B.cereus s. s. This highlights the intermingled taxonomy of B. cereus sensu lato group, where genomics alone does not support the present taxonomy between B. cereus s. s. and B. thuringiensis as species designation currently relies solely on the presence of entomocidal genes. ImportanceBacillus cereus group species have been extensively studied due to their economical and clinical relevance. This importance originally set the basis for B. cereus group members classification which are commonly based on phenotypical criteria. Sequencing era has shed light about genomic characterization of these species, showing their chromosomal genomic similarity and highlighting the role of mobile genetic elements, especially megaplasmids, in the classification and characterization of this group. However, only the 5% of the sequenced B. thuringiensis genomes have been fully resolved. Thus, here we addressed efficiently the study B. thuringiensis HER1410 genomic features by the use of a combination of short and long-reads sequencing. This methodology resulted in the high-quality assembly, which led to the identification of an uncommon location of a cry gene close to the chromosomal origin, as well as three fully resolved extrachromosomal elements, two megaplasmids and an integrative plasmidial prophage.

microbiology↗