Article
Biotechnology & Applied Microbiology
John R. Prensner, Oana M. Enache, Victor Luria, Karsten Krug, Karl R. Clauser, Joshua M. Dempster, Amir Karger, Li Wang, Karolina Stumbraite, Vickie M. Wang, Ginevra Botta, Nicholas J. Lyons, Amy Goodale, Zohra Kalani, Briana Fritchman, Adam Brown, Douglas Alan, Thomas Green, Xiaoping Yang, Jacob D. Jaffe, Jennifer A. Roth, Federica Piccioni, Marc W. Kirschner, Zhe Ji, David E. Root, Todd R. Golub
Summary: Noncanonical open reading frames have been shown to play essential roles in cancer cell function, encoding biologically active proteins that could serve as potential therapeutic targets. These findings suggest new avenues for the treatment of breast cancer.
NATURE BIOTECHNOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Chenxiao Xue, Caixia Cao
Summary: By using CRISPR-Cas base editing and prime editing, we manipulated upstream open reading frames - eukaryotic translational control elements - in rice to regulate translation levels. This enabled predictable and desired downregulation of gene expression, leading to quantitative phenotypic changes and crop improvement.
NATURE BIOTECHNOLOGY
(2023)
Article
Biochemical Research Methods
Bo Song, Hao Li, Mengyun Jiang, Zhongtian Gao, Suikang Wang, Lei Gao, Yunsheng Chen, Wujiao Li
Summary: In this study, a tool called slORFfinder was developed to identify slORFs by linking the spliced leader sequences to the recipient mRNAs and predicting slORFs based on the distribution of ribosome-protected footprints (RPFs). Applying this tool to nematodes, ascidians, and euglena, it was found that slORFs are widely present in these taxa and are generally translated at high levels, suggesting their potential important functions.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Annika Nelde, Lea Floetotto, Lara Juergens, Laura Szymik, Elvira Hubert, Jens Bauer, Christoph Schliemann, Torsten Kessler, Georg Lenz, Hans-Georg Rammensee, Juliane S. Walz, Klaus Wethmar
Summary: This study provides experimental evidence for the translational regulation of cancer-associated genes through uORFs, and demonstrates the frequent expression and occasional specific localization of uORF-derived peptides. Immunopeptidome analysis identified a set of naturally presented uORF-derived peptides, some of which are tumor-associated and capable of inducing multifunctional T cell responses. These findings suggest a potentially widespread function of uORFs and uPeptides in cancer biology.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Virology
Morgan Monaghan, Joshua Munger
Summary: Transposon-based insertional mutagenesis screens have shown that disruption of HCMV UL30 gene inhibits viral replication. Deletion of the canonical UL30 ORF reduces production of infectious virus, while comutation of methionines in the UL30 region and mutation of the TATA box lead to viral replication defects. The UL30-associated ORFs play an important role in HCMV infection and further research could provide insights for therapeutic interventions.
JOURNAL OF VIROLOGY
(2021)
Review
Plant Sciences
K. Bharathan Sruthi, Athira Menon, P. Akash, Eppurath Soniya
Summary: Long non-coding RNAs (lncRNAs) are RNA transcripts longer than 200 nucleotides without coding potential. Recent research shows that lncRNAs can code for micropeptides, which are generated from small open reading frames (smORFs) and found in short mRNAs and non-coding RNAs. Although micropeptides play critical roles in plant development and stress, only a few functions have been verified so far.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Hitesh Kore, Keshava K. Datta, Shivashankar H. Nagaraj, Harsha Gowda
Summary: Recent studies have discovered many proteins encoded by noncoding regions in the human genome. These proteins are often encoded by small open reading frames in the UTRs of mRNAs and lncRNAs, and show poor evolutionary conservation. Some of them have been functionally characterized and play important roles in fundamental biological processes and human diseases. The number of novel protein coding regions in the human genome and their functional importance remain unknown.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Virology
Rekha Dhanwani, Sandeep Kumar Dhanda, John Pham, Gregory P. Williams, John Sidney, Alba Grifoni, Gaelle Picarda, Cecilia S. Lindestam Arlehamn, Alessandro Sette, Chris A. Benedict
Summary: This study systematically analyzed the CMV ORFeome to identify new CMV epitopes targeted primarily by CD4 T cells in humans, identifying over 200 new T cell epitopes derived from both canonical and novel ORFs. The findings highlight the substantial breadth of the anti-CMV T cell response and provide new targets for vaccine design.
JOURNAL OF VIROLOGY
(2021)
Article
Genetics & Heredity
Chaitanya Erady, Adam Boxall, Shraddha Puntambekar, N. Suhas Jagannathan, Ruchi Chauhan, David Chong, Narendra Meena, Apurv Kulkarni, Bhagyashri Kasabe, Kethaki Prathivadi Bhayankaram, Yagnesh Umrania, Adam Andreani, Jean Nel, Matthew T. Wayland, Cristina Pina, Kathryn S. Lilley, Sudhakaran Prabakaran
Summary: The study identified novel open reading frames (nORFs) in cancer transcriptomes, showing extensive dysregulation at the transcript level and potential prognostic value. A subset of nORFs were associated with overall patient survival. Additionally, nORF products were found to form protein-like structures and in silico screening identified potential inhibitors against nORF-encoded proteins disrupted in stomach and esophageal cancer.
NPJ GENOMIC MEDICINE
(2021)
Article
Medicine, Research & Experimental
Caishang Zheng, Yanjun Wei, Peng Zhang, Longyong Xu, Zhenzhen Zhang, Kangyu Lin, Jiakai Hou, Xiangdong Lv, Yao Ding, Yulun Chiu, Antrix Jain, Nelufa Islam, Anna Malovannaya, Yun Wu, Feng Ding, Han Xu, Ming Sun, Xi Chen, Yiwen Chen
Summary: Emerging evidence shows that cryptic translation within lncRNAs may produce new proteins with important functions. In this study, researchers found that estrogen receptor alpha-positive breast cancer depends on the cryptic ORFs encoded by upregulated lncRNA genes. They identified an unannotated protein, GT3-INCP, which promotes tumor growth and is associated with poor prognosis in luminal tumors. Mechanistically, GT3-INCP interacts with GATA3, a transcription factor important in mammary gland development and breast cancer cell proliferation, and regulates the expression of genes involved in estrogen response and cell proliferation.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Maximilian P. Kohl, Maria Kompatscher, Nina Clementi, Lena Holl, Matthias D. Erlacher
Summary: This study investigates the important factors in start codon recognition during translation initiation and discovers the existence of an ambiguous translation initiation mechanism, which may lead to the identification of unrecognized ORFs and translation products in bacteria.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Caishang Zheng, Yanjun Wei, Peng Zhang, Kangyu Lin, Dandan He, Hongqi Teng, Ganiraju Manyam, Zhao Zhang, Wen Liu, Hye Rin Lindsay Lee, Ximing Tang, Wei He, Nelufa Islam, Antrix Jain, Yulun Chiu, Shaolong Cao, Yarui Diao, Sherita Meyer-Gauen, Magnus Hoeoek, Anna Malovannaya, Wenbo Li, Ming Hu, Wenyi Wang, Han Xu, Scott Kopetz, Yiwen Chen
Summary: Cryptic non-canonical open reading frames (ORFs) encode proteins that play important roles in colorectal cancer. The microprotein SMIMP regulates the binding of cohesin to cis-regulatory elements, promoting tumor formation.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Plant Sciences
Miryam A. Cymerman, Helen Saul, Ronit Farhi, Karina Vexler, Dror Gottlieb, Irina Berezin, Orit Shaul
Summary: Translated upstream open reading frames (uORFs) can inhibit the translation of main open reading frames (ORFs) and lead to transcript degradation in eukaryotic cells. In mammalian cells, the length, structure, and reinitiation efficiency of translated uORFs play important roles in determining whether the transcripts will be targeted for degradation by the nonsense-mediated mRNA decay (NMD) pathway. However, the significance of these factors in NMD targeting for plants is still not well-studied.
JOURNAL OF EXPERIMENTAL BOTANY
(2023)
Review
Biochemistry & Molecular Biology
Petr V. Sergiev, Maria P. Rubtsova
Summary: Cell functioning is a tightly regulated process, with recent studies revealing that short open reading frames play functional roles in regulating the stability and translational efficiency of the main reading frame. The advancement in proteomic analysis methods has allowed for the identification of translation products from short open reading frames, indicating their potential functional roles in cell regulation and adaptation to changing conditions.
BIOCHEMISTRY-MOSCOW
(2021)