Alternative splicing of type II procollagen: IIB or not IIB?
Alternative splicing of type II procollagen: IIB or not IIB?
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DOI：
10.3109/03008207.2014.908860
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发表时间：
2014-06
影响因子：
2.9
通讯作者：
McAlinden A
中科院分区：
文献类型：
--
作者：
McAlinden A
二十多年前，II型前胶原基因(COL2A1)的两种亚型被发现。这些异构体命名为IIA和IIB，通过外显子2的选择性剪接以发育调节的方式产生。软骨前体细胞主要合成IIA异构体(含外显子2)，而分化的软骨细胞主要合成IIB转录本(不含外显子2)。重要的是，这种从IIA到IIB的选择性剪接开关只发生在软骨形成过程中。最近，还报道了另外两种异构体(IIC和IID)，它们也涉及外显子2的剪接；这些发现突显了涉及COL2A1表达调控的复杂性。为什么COL2A1的不同亚型存在于骨骼发育和维持的背景下，其生物学意义仍然不完全清楚。该综述将提供COL2A1亚型在软骨细胞分化过程中表达的最新知识，以及关于控制外显子2选择性剪接的一些机制的已知情况。还将讨论利用小鼠模型来解决体内Col2a1选择性剪接的生物学意义。根据目前所获得的知识，现在提出了一些新的问题和概念，涉及Col2a1选择性剪接在调节细胞外基质组装中的重要性，以及这可能随后如何影响软骨和软骨内骨的质量和功能。
Over two decades ago, two isoforms of the type II procollagen gene (COL2A1) were discovered. These isoforms, named IIA and IIB, are generated in a developmentally-regulated manner by alternative splicing of exon 2. Chondroprogenitor cells synthesize predominantly IIA isoforms (containing exon 2) while differentiated chondrocytes produce mainly IIB transcripts (devoid of exon 2). Importantly, this IIA-to-IIB alternative splicing switch occurs only during chondrogenesis. More recently, two other isoforms have been reported (IIC and IID) that also involve splicing of exon 2; these findings highlight the complexities involving regulation of COL2A1 expression. The biological significance of why different isoforms of COL2A1 exist within the context of skeletal development and maintenance is still not completely understood. This review will provide current knowledge on COL2A1 isoform expression during chondrocyte differentiation and what is known about some of the mechanisms that control exon 2 alternative splicing. Utilization of mouse models to address the biological significance of Col2a1 alternative splicing in vivo will also be discussed. From the knowledge acquired to date, some new questions and concepts are now being proposed on the importance of Col2a1 alternative splicing in regulating extracellular matrix assembly and how this may subsequently affect cartilage and endochondral bone quality and function.
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影响因子：
14.9
作者：
Cartegni, L;Wang, JH;Krainer, AR
通讯作者：
Krainer, AR
影响因子：
2.7
作者：
Duran, I.;Mari-Beffa, M.;Santos-Ruiz, L.
通讯作者：
Santos-Ruiz, L.
影响因子：
4.8
作者：
Fukui, N;McAlinden, A;Sandell, LJ
通讯作者：
Sandell, LJ
DOI：
10.1016/s0006-291x(79)80024-8
发表时间：
1979-01-01
影响因子：
3.1
作者：
BURGESON, RE;HOLLISTER, DW
通讯作者：
HOLLISTER, DW
DOI：
10.1186/ar380
发表时间：
2002
期刊：
Arthritis research
影响因子：
--
作者：
Eyre D
通讯作者：
Eyre D