journal
https://read.qxmd.com/read/38759625/g-quadruplex-folding-in-xist-rna-antagonizes-prc2-activity-for-stepwise-regulation-of-x-chromosome-inactivation
#41
JOURNAL ARTICLE
Yong Woo Lee, Uri Weissbein, Roy Blum, Jeannie T Lee
How Polycomb repressive complex 2 (PRC2) is regulated by RNA remains an unsolved problem. Although PRC2 binds G-tracts with the potential to form RNA G-quadruplexes (rG4s), whether rG4s fold extensively in vivo and whether PRC2 binds folded or unfolded rG4 are unknown. Using the X-inactivation model in mouse embryonic stem cells, here we identify multiple folded rG4s in Xist RNA and demonstrate that PRC2 preferentially binds folded rG4s. High-affinity rG4 binding inhibits PRC2's histone methyltransferase activity, and stabilizing rG4 in vivo antagonizes H3 at lysine 27 (H3K27me3) enrichment on the inactive X chromosome...
May 16, 2024: Molecular Cell
https://read.qxmd.com/read/38759624/genomic-context-sensitizes-regulatory-elements-to-genetic-disruption
#42
JOURNAL ARTICLE
Raquel Ordoñez, Weimin Zhang, Gwen Ellis, Yinan Zhu, Hannah J Ashe, André M Ribeiro-Dos-Santos, Ran Brosh, Emily Huang, Megan S Hogan, Jef D Boeke, Matthew T Maurano
Genomic context critically modulates regulatory function but is difficult to manipulate systematically. The murine insulin-like growth factor 2 (Igf2)/H19 locus is a paradigmatic model of enhancer selectivity, whereby CTCF occupancy at an imprinting control region directs downstream enhancers to activate either H19 or Igf2. We used synthetic regulatory genomics to repeatedly replace the native locus with 157-kb payloads, and we systematically dissected its architecture. Enhancer deletion and ectopic delivery revealed previously uncharacterized long-range regulatory dependencies at the native locus...
May 16, 2024: Molecular Cell
https://read.qxmd.com/read/38759623/a-parp1-timeless-alliance-in-cancer-therapy
#43
JOURNAL ARTICLE
Madalena Tarsounas
In a recent paper in Nature, Petropoulos et al.1 report that PARP1 acts together with the replisome components TIMELESS and TIPIN to protect the genome from transcription-replication conflicts, which has important implications for the clinical use of PARP inhibitors.
May 16, 2024: Molecular Cell
https://read.qxmd.com/read/38759622/getting-membrane-proteins-into-shape
#44
JOURNAL ARTICLE
Ramanujan S Hegde
In this issue, Ji et al.1 show how a multipass membrane protein that initially inserts into the endoplasmic reticulum in a mostly inverted topology is post-translationally dislocated, re-inserted, and folded with the help of ATP13A1, a P-type ATPase.
May 16, 2024: Molecular Cell
https://read.qxmd.com/read/38759621/cysteine-substitutants-emerge-in-lung-cancer-proteomes-during-arginine-restriction
#45
JOURNAL ARTICLE
Dennis J Hsu, Sohail F Tavazoie
In this issue of Molecular Cell, Yang et al.1 find that arginine-to-cysteine substitutants are enriched in a subset of lung cancer proteomes, potentiated by arginine deprivation, and promote resistance to chemotherapy.
May 16, 2024: Molecular Cell
https://read.qxmd.com/read/38701743/energy-sensor-ampk-gamma-regulates-translation-via-phosphatase-ppp6c-independent-of-ampk-alpha
#46
Qi Zhou, Bingbing Hao, Xiaolei Cao, Lin Gao, Zhenyue Yu, Yang Zhao, Mingrui Zhu, Guoxuan Zhong, Fangtao Chi, Xiaoming Dai, Jizhong Mao, Yibing Zhu, Ping Rong, Liang Chen, Xueli Bai, Cunqi Ye, Shuai Chen, Tingbo Liang, Li Li, Xin-Hua Feng, Minjia Tan, Bin Zhao
No abstract text is available yet for this article.
May 2, 2024: Molecular Cell
https://read.qxmd.com/read/38701742/on-the-covalent-nature-of-lysine-polyphosphorylation
#47
JOURNAL ARTICLE
Cristina Azevedo, Filipy Borghi, Xue Bessie Su, Adolfo Saiardi
Post-translational modifications of proteins (PTMs) introduce an extra layer of complexity to cellular regulation. Although phosphorylation of serine, threonine, and tyrosine residues is well-known as PTMs, lysine is, in fact, the most heavily modified amino acid, with over 30 types of PTMs on lysine having been characterized. One of the most recently discovered PTMs on lysine residues is polyphosphorylation, which sees linear chains of inorganic polyphosphates (polyP) attached to lysine residues. The labile nature of phosphoramidate bonds raises the question of whether this modification is covalent in nature...
May 2, 2024: Molecular Cell
https://read.qxmd.com/read/38701741/polyphosphate-attachment-to-lysine-repeats-is-a-non-covalent-protein-modification
#48
JOURNAL ARTICLE
Nolan Neville, Kirsten Lehotsky, Kody A Klupt, Michael Downey, Zongchao Jia
Polyphosphate (polyP) is a chain of inorganic phosphate that is present in all domains of life and affects diverse cellular phenomena, ranging from blood clotting to cancer. A study by Azevedo et al. described a protein modification whereby polyP is attached to lysine residues within polyacidic serine and lysine (PASK) motifs via what the authors claimed to be covalent phosphoramidate bonding. This was based largely on the remarkable ability of the modification to survive extreme denaturing conditions...
May 2, 2024: Molecular Cell
https://read.qxmd.com/read/38701740/keeping-cgas-in-check-spsb3-promotes-nuclear-cgas-degradation-for-maintaining-immune-homeostasis
#49
JOURNAL ARTICLE
Ruey-Hwa Chen
In a recent publication in Nature, Xu et al.1 discovered a role of CRL5-SPSB3 ubiquitin ligase in promoting ubiquitination and degradation of nuclear cGAS, which prevents aberrant cGAS activation by genomic DNA and contributes to the maintenance of immune homeostasis.
May 2, 2024: Molecular Cell
https://read.qxmd.com/read/38701739/eif4g-as-a-switch-for-heat-shock-mrna-translation
#50
COMMENT
Yi Liu, Peiguo Yang
The heat shock response is crucial for cell survival. In this issue of Molecular Cell, Desroches Altamirano et al.1 demonstrate that a temperature-induced conformational change in the translation initiation factor eIF4G is a key mechanism regulating translation during the heat shock response.
May 2, 2024: Molecular Cell
https://read.qxmd.com/read/38701738/ddx21-the-link-between-m-6-a-and-r-loops
#51
COMMENT
Guillaume Lavergne, Jean-Yves Roignant
In this issue of Molecular Cell, Hao et al.1 demonstrate that the RNA helicase DDX21 recruits the m6 A methyltransferase complex to R-loops, ensuring proper transcription termination and genome stability.
May 2, 2024: Molecular Cell
https://read.qxmd.com/read/38701737/response-to-energy-sensor-ampk%C3%AE-does-not-exist-in-isolation-from-ampk%C3%AE-or-interact-with-ppp6c-in-muscle-and-liver-from-humans-and-mice
#52
LETTER
Qi Zhou, Xiaolei Cao, Bin Zhao
No abstract text is available yet for this article.
May 2, 2024: Molecular Cell
https://read.qxmd.com/read/38701736/energy-sensor-ampk%C3%AE-does-not-exist-in-isolation-from-ampk%C3%AE-or-interact-with-ppp6c-in-muscle-and-liver-from-humans-and-mice
#53
LETTER
Rasmus Kjøbsted, Jesper Bratz Birk, Nicolas Oldenburg Eskesen, Jørgen Frank Pind Wojtaszewski
No abstract text is available yet for this article.
May 2, 2024: Molecular Cell
https://read.qxmd.com/read/38593806/time-resolved-profiling-of-rna-binding-proteins-throughout-the-mrna-life-cycle
#54
JOURNAL ARTICLE
Yeon Choi, Buyeon Um, Yongwoo Na, Jeesoo Kim, Jong-Seo Kim, V Narry Kim
mRNAs continually change their protein partners throughout their lifetimes, yet our understanding of mRNA-protein complex (mRNP) remodeling is limited by a lack of temporal data. Here, we present time-resolved mRNA interactome data by performing pulse metabolic labeling with photoactivatable ribonucleoside in human cells, UVA crosslinking, poly(A)+ RNA isolation, and mass spectrometry. This longitudinal approach allowed the quantification of over 700 RNA binding proteins (RBPs) across ten time points. Overall, the sequential order of mRNA binding aligns well with known functions, subcellular locations, and molecular interactions...
May 2, 2024: Molecular Cell
https://read.qxmd.com/read/38640897/retraction-notice-to-human-dna-polymerase-%C3%AE-harbors-dna-end-trimming-activity-critical-for-dna-repair
#55
JOURNAL ARTICLE
Karl E Zahn, Ryan B Jensen, Richard D Wood, Sylvie Doublie
No abstract text is available yet for this article.
April 18, 2024: Molecular Cell
https://read.qxmd.com/read/38640896/detection-of-ac4c-in-human-mrna-is-preserved-upon-data-reassessment
#56
JOURNAL ARTICLE
Hamid Beiki, David Sturgill, Daniel Arango, Sebastien Relier, Sarah Schiffers, Shalini Oberdoerffer
We recently reported the distribution of N4-acetylcytidine (ac4C) in HeLa mRNA at base resolution through chemical reduction and the induction of C:T mismatches in sequencing (RedaC:T-seq). Our results contradicted an earlier report from Schwartz and colleagues utilizing a similar method termed ac4C-seq. Here, we revisit both datasets and reaffirm our findings. Through RedaC:T-seq reanalysis, we establish a low basal error rate at unmodified nucleotides that is not skewed to any specific mismatch type and a prominent increase in C:T substitutions as the dominant mismatch type in both treated wild-type replicates, with a high degree of reproducibility across replicates...
April 18, 2024: Molecular Cell
https://read.qxmd.com/read/38640895/no-evidence-for-ac4c-within-human-mrna-upon-data-reassessment
#57
JOURNAL ARTICLE
Joseph Georgeson, Schraga Schwartz
Cytidine acetylation (ac4C) of RNA is a post-transcriptional modification catalyzed by Nat10. Recently, an approach termed RedaC:T was employed to map ac4C in human mRNA, relying on detection of C>T mutations in WT but not in Nat10-KO cells. RedaC:T suggested widespread ac4C presence. Here, we reanalyze RedaC:T data. We find that mismatch signatures are not reproducible, as C>T mismatches are nearly exclusively present in only one of two biological replicates. Furthermore, all mismatch types-not only C>T-are highly enriched in WT samples, inconsistent with an acetylation signature...
April 18, 2024: Molecular Cell
https://read.qxmd.com/read/38640894/sequential-requirements-for-distinct-pol%C3%AE-domains-during-theta-mediated-end-joining
#58
JOURNAL ARTICLE
Carel Fijen, Lea Drogalis Beckham, Dante Terino, Yuzhen Li, Dale A Ramsden, Richard D Wood, Sylvie Doublié, Eli Rothenberg
DNA polymerase θ (Polθ) plays a central role in a DNA double-strand break repair pathway termed theta-mediated end joining (TMEJ). TMEJ functions by pairing short-sequence "microhomologies" (MHs) in single-stranded DNA at each end of a break and subsequently initiating DNA synthesis. It is not known how the Polθ helicase domain (HD) and polymerase domain (PD) operate to bring together MHs and facilitate repair. To resolve these transient processes in real time, we utilized in vitro single-molecule FRET approaches and biochemical analyses...
April 18, 2024: Molecular Cell
https://read.qxmd.com/read/38640893/shining-light-on-dhx9-uv-induced-stress-granules-illuminate-protective-mechanisms-for-daughter-cell-resilience
#59
JOURNAL ARTICLE
Dylan M Parker, Gaia R Bublitz, Roy Parker
In a recent article in Cell, Zhou et al. investigate the origins, composition, and biological consequences of UV-induced stress granules. They find that UV-induced stress granules are triggered by the formation of RNA-protein crosslinks, uniquely contain DHX9 as a marker, form during mitosis independently of translation repression, and are enriched in intron-containing RNAs and splicing factors. Moreover, UV-induced granules contain double-stranded RNA (dsRNA) and trigger a dsRNA response. This work identifies a mechanism for resolving UV-damaged RNA and broadens the types of cytosolic "stress granules" that form...
April 18, 2024: Molecular Cell
https://read.qxmd.com/read/38640892/free-ribosomal-proteins-as-culprits-for-nucleolar-stress
#60
JOURNAL ARTICLE
Ina Huppertz
Nucleolar stress has been consistently linked to age-related diseases. In this issue, Sirozh et al.1 find that the common molecular signature of nucleolar stress is the accumulation of free ribosomal proteins, which leads to premature aging in mice; however, it can be reversed by mTOR inhibition.
April 18, 2024: Molecular Cell
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