Niewiadomska, E. | Search bioRxiv

bioRxiv2024

Toss GERALT into chloroplast to make it green: a new regulator of chloroplast biogenesis and chlorophyll biosynthesis

Proteins belonging into cryptochrome/photolyase family act as either blue light photoreceptors or as enzymes responsible for repair of pyrimidine dimers produced under UV. Surprisingly, the members of plant-specific photolyase/blue-light receptor 2 (PPL/PHR2) subclade of this family, are almost completely uncharacterized. Here, we focused on the physiological role of protein encoded by Arabidopsis At2g47590 gene. Our results demonstrate for the first time its crucial role in cotyledon greening and maintenance of plant fitness. Based on the phenotype of the mutant in At2g47590 gene i.e. albino cotyledons and pale green true leaves we named this gene GERALT (GERMINATION ALBINO TRANSIENT). Using different approach including analysis of plant phenotypes, chloroplast sizes and architecture, transcriptomes, photosynthetic pigments, maximum PSII quantum yield (FV/FM) we show that the proper plant functioning is the effect of co-operation of GERALT-dependent and -independent pathways with the role of the former diminishing with plant age. Lower levels of transcripts dependent on plastid encoded polymerase and higher levels of these dependent on nuclear encoded polymerase, smaller chloroplasts with large grana stacks and very weakly developed stromal thylakoids, lower levels of photosynthetic pigments with higher chlorophyll a/b ratio, are among characteristic features of geralt plants. We believe that these results encourage scientific community to study PPL/PHR2 proteins which seems to play a special role in plants.

plant biology↗

bioRxiv2018

The Genetic Landscape of Diamond-Blackfan Anemia

Diamond-Blackfan anemia (DBA) is a rare bone marrow failure disorder that affects 1 in 100,000 to 200,000 live births and has been associated with mutations in components of the ribosome. In order to characterize the genetic landscape of this genetically heterogeneous disorder, we recruited a cohort of 472 individuals with a clinical diagnosis of DBA and performed whole exome sequencing (WES). Overall, we identified rare and predicted damaging mutations in likely causal genes for 78% of individuals. The majority of mutations were singletons, absent from population databases, predicted to cause loss of function, and in one of 19 previously reported genes encoding for a diverse set of ribosomal proteins (RPs). Using WES exon coverage estimates, we were able to identify and validate 31 deletions in DBA associated genes. We also observed an enrichment for extended splice site mutations and validated the diverse effects of these mutations using RNA sequencing in patientderived cell lines. Leveraging the size of our cohort, we observed several robust genotype-phenotype associations with congenital abnormalities and treatment outcomes. In addition to comprehensively identifying mutations in known genes, we further identified rare mutations in 7 previously unreported RP genes that may cause DBA. We also identified several distinct disorders that appear to phenocopy DBA, including 9 individuals with biallelic CECR1 mutations that result in deficiency of ADA2. However, no new genes were identified at exome-wide significance, suggesting that there are no unidentified genes containing mutations readily identified by WES that explain > 5% of DBA cases. Overall, this comprehensive report should not only inform clinical practice for DBA patients, but also the design and analysis of future rare variant studies for heterogeneous Mendelian disorders.

genetics↗