TY  - JOUR
A1  - Wencker, Freya D. R
A1  - Marincola, Gabriella
A1  - Schoenfelder, Sonja M. K.
A1  - Maaß, Sandra
A1  - Becher, Dörte
A1  - Ziebuhr, Wilma
T1  - Another layer of complexity in Staphylococcus aureus methionine biosynthesis control: unusual RNase III-driven T-box riboswitch cleavage determines met operon mRNA stability and decay
JF  - Nucleic Acids Research
N2  - In Staphylococcus aureus, de novo methionine biosynthesis is regulated by a unique hierarchical pathway involving stringent-response controlled CodY repression in combination with a T-box riboswitch and RNA decay. The T-box riboswitch residing in the 5′ untranslated region (met leader RNA) of the S. aureus metICFE-mdh operon controls downstream gene transcription upon interaction with uncharged methionyl-tRNA. met leader and metICFE-mdh (m)RNAs undergo RNase-mediated degradation in a process whose molecular details are poorly understood. Here we determined the secondary structure of the met leader RNA and found the element to harbor, beyond other conserved T-box riboswitch structural features, a terminator helix which is target for RNase III endoribonucleolytic cleavage. As the terminator is a thermodynamically highly stable structure, it also forms posttranscriptionally in met leader/ metICFE-mdh read-through transcripts. Cleavage by RNase III releases the met leader from metICFE-mdh mRNA and initiates RNase J-mediated degradation of the mRNA from the 5′-end. Of note, metICFE-mdh mRNA stability varies over the length of the transcript with a longer lifespan towards the 3′-end. The obtained data suggest that coordinated RNA decay represents another checkpoint in a complex regulatory network that adjusts costly methionine biosynthesis to current metabolic requirements.
KW  - allelic replacement
KW  - expression
KW  - translation
KW  - mechanism
KW  - acid
KW  - endoribonuclease
KW  - antitermination
KW  - transcription
KW  - proteins
KW  - geometry
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259029
VL  - 49
IS  - 4
ER  - 
TY  - JOUR
A1  - Wagner, Ines
A1  - Volkmer, Michael
A1  - Sharan, Malvika
A1  - Villaveces, Jose M.
A1  - Oswald, Felix
A1  - Surendranath, Vineeth
A1  - Habermann, Bianca H.
T1  - morFeus: a web-based program to detect remotely conserved orthologs using symmetrical best hits and orthology network scoring
JF  - BMC Bioinformatics
N2  - Background: Searching the orthologs of a given protein or DNA sequence is one of the most important and most commonly used Bioinformatics methods in Biology. Programs like BLAST or the orthology search engine Inparanoid can be used to find orthologs when the similarity between two sequences is sufficiently high. They however fail when the level of conservation is low. The detection of remotely conserved proteins oftentimes involves sophisticated manual intervention that is difficult to automate. 
Results: Here, we introduce morFeus, a search program to find remotely conserved orthologs. Based on relaxed sequence similarity searches, morFeus selects sequences based on the similarity of their alignments to the query, tests for orthology by iterative reciprocal BLAST searches and calculates a network score for the resulting network of orthologs that is a measure of orthology independent of the E-value. Detecting remotely conserved orthologs of a protein using morFeus thus requires no manual intervention. We demonstrate the performance of morFeus by comparing it to state-of-the-art orthology resources and methods. We provide an example of remotely conserved orthologs, which were experimentally shown to be functionally equivalent in the respective organisms and therefore meet the criteria of the orthology-function conjecture. 
Conclusions: Based on our results, we conclude that morFeus is a powerful and specific search method for detecting remotely conserved orthologs.
KW  - reciprocal best hit
KW  - finder using symmetrical best hits
KW  - sequences
KW  - annotation
KW  - identification
KW  - database
KW  - genomes
KW  - proteins
KW  - homologs
KW  - hidden markov-models
KW  - phylogenetic trees
KW  - PSI-blast
KW  - eigenvector centrality
KW  - meta-analysis based orthology
KW  - orthology
KW  - remote sequence conservation
KW  - alignment clustering
KW  - orthology network
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115590
VL  - 15
IS  - 263
ER  -