CD47 is an immunoglobulin that is overexpressed on the surface of many types of cancer cells. CD47 forms a signaling complex with signal-regulatory protein α (SIRPα), enabling the escape of these cancer cells from macrophage-mediated phagocytosis. In recent years, CD47 has been shown to be highly expressed by various types of solid tumors and to be associated with poor patient prognosis in various types of cancer. A growing number of studies have since demonstrated that inhibiting the CD47-SIRPα signaling pathway promotes the adaptive immune response and enhances the phagocytosis of tumor cells by macrophages. Improved understanding in this field of research could lead to the development of novel and effective anti-tumor treatments that act through the inhibition of CD47 signaling in cancer cells. In this review, we describe the structure and function of CD47, provide an overview of studies that have aimed to inhibit CD47-dependent avoidance of macrophage-mediated phagocytosis by tumor cells, and assess the potential and challenges for targeting the CD47-SIRPα signaling pathway in anti-cancer therapy.

The 3 0 untranslated region (3 0 UTR) of turnip crinkle virus (TCV) genomic RNA contains a cap-independent translation element (CITE), which includes a ribosome-binding structural element (RBSE) that participates in recruitment of the large ribosomal subunit. In addition, a large symmetric loop in the RBSE plays a key role in coordinating the incompatible processes of viral translation and replication, which require enzyme progression in opposite directions on the viral template. To understand the structural basis for the large ribosomal subunit recruitment and the intricate interplay among different parts of the molecule, we determined the global structure of the 102-nt RBSE RNA using solution NMR and small-angle x-ray scattering. This RNA has many structural features that resemble those of a tRNA in solution. The hairpins H1 and H2, linked by a 7-nucleotide linker, form the upper part of RBSE and hairpin H3 is relatively independent from the rest of the structure and is accessible to interactions. This global structure provides insights into the three-dimensional layout for ribosome binding, which may serve as a structural basis for its involvement in recruitment of the large ribosomal subunit and the switch between viral translation and replication. The experimentally determined threedimensional structure of a functional element in the 3 0 UTR of an RNA from any organism has not been previously reported. The RBSE structure represents a prototype structure of a new class of RNA structural elements involved in viral translation/replication processes.new method | NMR | SAXS | 3' UTR RNA | RNA structure S tructural elements in mRNAs such as the 5 0 cap, internal ribosome entry site in the 5 0 UTR, and the 3 0 poly(A) tail in the 3 0 UTR are important determinants for efficient translation initiation (1). These structural elements can function synergistically to attract ribosomes and translation factors to enhance translation initiation (2, 3). In both cap and poly(A) tail-dependent translation in eukaryotes this enhancement is realized by the binding factor elF4G associating with both the polyA binding protein (Pab1p) and elF4E, resulting in a circularized mRNA template (4), which has been visualized under atomic force microscopy (5). In contrast, high level initiation of capindependent translation in many plant viruses involves 3 0 UTR RNA elements known as CITE (6). TCV lacks a 5 0 cap and poly(A) tail. Instead the virus uses a structural element in its 3 0 UTR that synergistically enhances translation when associated with its 5 0 UTR (7) (Fig. 1A). A model for 3 0 UTR involvement in the recruitment of the large ribosomal subunit has been proposed to account for the enhancement (7) but the experimental structural basis for such an involvement has not been demonstrated. Moreover, mechanisms are required to temporally coordinate viral replication and translation because these processes are mutually exclusive due to the opposing directions of protein and RNA synthesis. The infecting genomic RNA must first be trans...

We report a "top-down" method that uses mainly duplexes' global orientations and overall molecular dimension and shape restraints, which were extracted from experimental NMR and small angle Xray scattering (SAXS) data respectively, to determine global architectures of RNA molecules consisting of mostly A-form like duplexes. The method is implemented in the G2G (from Global measurement to Global Structure) toolkit of programs. We demonstrate the efficiency and accuracy of the method by determining the global structure of a 71-nucleotide RNA using experimental data. The backbone root-mean-square-deviation (RMSD) of the ensemble of the calculated global structures relative to the X-ray crystal structure using the experimental data is 3.0 ± 0.3 Å, and the RMSD is only 2.5 ± 0.2 Å for the three duplexes that were orientation-restrained during the calculation. The global structure simplifies interpretation of multi-dimensional nuclear Overhauser spectra for high resolution structure determination. The potential general application of the method for RNA structure determination is discussed.To whom correspondence should be addressed: Y-X Wang: wangyu@ncifcrf.gov, (phone) 301-846-5985. * These authors contributed equally to this work & Current address: Gynecology and Obstetric Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011, People's Republic of China Supporting Information Available: A more detailed description of the methods and materials, including a detailed description of the G2G toolkit is provided in the Supporting Information. The calculation protocols, and the G2G toolkit package, all data files together with the coordinates and restraint filescan also be downloaded from the authors' web sites http://xxx.